Matrix-assisted laser desorption/ionization (MALDI) is a soft ionization technique used in mass spectrometry, allowing the analysis of biomolecules (biopolymers such as proteins, peptides and sugars) and large organic molecules (such as polymers, dendrimers and other macromolecules), which tend to be fragile and fragment when ionized by more conventional ionization methods. It is most similar in character to electrospray ionization both in relative softness and the ions produced (although it causes many fewer multiply charged ions).

The ionization is triggered by a laser beam (normally a nitrogen laser). A matrix is used to protect the biomolecule from being destroyed by direct laser beam and to facilitate vaporization and ionization.

Mass Spectometry
The type of a mass spectrometer most widely used with MALDI is the TOF (time-of-flight mass spectrometer), mainly due to its large mass range. The TOF measurement procedure is also ideally suited to the MALDI ionization process since the pulsed laser takes individual 'shots' rather than working in continuous operation. MALDI-TOF instruments are typically equipped with an "ion mirror", deflecting ions with an electric field, thereby doubling the ion flight path and increasing the resolution. Today, commercial reflectron TOF instruments reach a resolving power m/Δm of well above 20'000 FWHM (full-width half-maximum, Δm defined as the peak width at 50% of peak height).

MALDI has been coupled with IMS-TOF MS to identify phoshorylated and non-phosphorylated peptides .

MALDI-FT-ICR MS has been demonstrated to be a useful technique where high resolution MALDI-MS measurements are desired

In proteomics, MALDI is used for the identification of proteins isolated through gel electrophoresis: SDS-PAGE, size exclusion chromatography, and two-dimensional gel electrophoresis. One method used is peptide mass fingerprinting by MALDI-MS, or with post ionisation decay or collision-induced dissociation (further use see mass spectrometry).

Loss of sialic acid has been identified in papers when DHB has been used as a matrix for MALDI MS analysis of glycosylated peptides. Using sinapinic acid, 4-HCCA and DHB as matrices, Dr. Martin studied loss of sialic acid in glycosylated peptides by metastable decay in MALDI/TOF in linear mode and reflector mode . A group at SHIMIZU CORPORATION proposed derivitizing the sialic acid by an amidation reaction as a way to improve results  and also proposed use of an Ionic liquid matrix to reduce loss of sialic acid during MALDI/TOF MS analysis of sialylated oligosaccharides . THAP , DHAP , and a mixture of 2-aza-2-thiothymine and phenylhydrazine have been identified as matrices that could be used to minimize loss of sialic acid during MALDI MS analysis of glycosylated peptides.

It has been reported that a reduction in loss of some post-translational modifications can be accomplished if IR MALDI is used instead of UV MALDI


The serotonin (5-hydroxytryptamine, 5-HT) receptors are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous system. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their endogenous ligand. The serotonin receptors modulate the release of many neurotransmitters, including glutamate, GABA, dopamine, epinephrine/norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin, cortisol, corticosterone, corticotropin, and substance P, among others. The serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, and thermoregulation. The serotonin receptors are the target of a variety of pharmaceutical and illicit drugs, including many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens.


Noradrenaline Animation

Noradrenaline (BAN) (abbreviated NA or NAd) or norepinephrine (INN) (abbreviated norepi or NE) is a catecholamine with dual roles as a hormone and a neurotransmitter.
As a stress hormone, norepinephrine affects parts of the brain where attention and responding actions are controlled. Along with epinephrine, norepinephrine also underlies the fight-or-flight response, directly increasing heart rate, triggering the release of glucose from energy stores, and increasing blood flow to skeletal muscle.

However, when norepinephrine acts as a drug it will increase blood pressure by its prominent increasing effects on the vascular tone from α-adrenergic receptor activation. The resulting increase in vascular resistance triggers a compensatory reflex that overcomes its direct stimulatory effects on the heart, called the baroreceptor reflex, which results in a drop in heart rate called reflex bradycardia.

Norepinephrine is synthesized from tyrosine as a precursor, and packed into synaptic vesicles. It performs its action by being released into the synaptic cleft, where it acts on adrenergic receptors, followed by the signal termination, either by degradation of norepinephrine, or by uptake by surrounding cells.

Norepinephrine is synthesized by a series of enzymatic steps in the adrenal medulla and postganglionic neurons of the sympathetic nervous system from the amino acid tyrosine:

The first reaction is the hydroxylation into dihydroxyphenylalanine (L-DOPA) (DOPA = 3,4-DiHydroxy-L-Phenylalanine), catalyzed by tyrosine hydroxylase. This is the rate-limiting step.

This is followed by decarboxylation into the neurotransmitter dopamine, catalyzed by pyridoxal phosphate & DOPA decarboxylase.

Last is the final β-oxidation into norepinephrine by dopamine beta hydroxylase, requiring ascorbate as a cofactor (electron donor).
Norepinephrine. (2009, December 11). In Wikipedia, The Free Encyclopedia. Retrieved 12:38, December 16, 2009, from

How SSRIs and MAO Inhibitors Work Animation

Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor (SSRIs) are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. They are also typically effective and used in treating premature ejaculation problems as well as some cases of insomnia.

SSRIs increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin available to bind to the postsynaptic receptor. They have varying degrees of selectivity for the other monoamine transporters, with pure SSRIs having only weak affinity for the noradrenaline and dopamine transporter.

Mode of action
SSRIs are believed to act by inhibiting the reuptake of serotonin after being released in synapses. How much an individual will respond to this, however, also depends on genetics. In addition, several other mechanisms are suggested for the desired effect, e.g. neuroprotection and anti-inflammatory and immunomodulatory factors. Taken together, SSRI has several advantages compared with tricyclic antidepressants (TCA)s and 5-HT-prodrugs. However, the latter might be required in addition to SSRIs in certain situations.
Monoamine oxidase inhibitors (MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression, and have also shown efficacy in smoking cessation.

Due to potentially lethal dietary and drug interactions, MAOIs had been reserved as a last line of defense, used only when other classes of antidepressant drugs (for example selective serotonin reuptake inhibitors and tricyclic antidepressants) have failed. Recently, however, a patch form of the drug selegiline, called Emsam, was developed. It was approved for use by the FDA on February 28, 2006. When applied transdermally the drug does not enter the gastro-intestinal system as it does when taken orally, thereby decreasing the dangers of dietary interactions associated with MAOI pills.


Bioenergetics is the subject of a field of biochemistry that concerns energy flow through living systems. This is an active area of biological research that includes the study of thousands of different cellular processes such as cellular respiration and the many other metabolic processes that can lead to production and utilization of energy in forms such as ATP molecules.

Works structure of the body from cells

Mismeasure of Man

Ralph Horwitz, MD, professor of medicine at Stanford discusses how measurement can both strengthen and weaken clinical science and care. Often overlooked amid today's enthusiasm for quantifiable results, he says, are the real complexities of medicine.

DNA Polymerase

DNA polymerase is an enzyme that catalyzes the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best-known for their role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand. The newly-polymerized molecule is complementary to the template strand and identical to the template's original partner strand. DNA polymerases use a magnesium ion for catalytic activity.

DNA polymerase can add free nucleotides to only the 3’ end of the newly-forming strand. This results in elongation of the new strand in a 5'-3' direction. No known DNA polymerase is able to begin a new chain (de novo). DNA polymerase can add a nucleotide onto only a preexisting 3'-OH group, and, therefore, needs a primer at which it can add the first nucleotide. Primers consist of RNA and DNA bases with the first two bases always being RNA, and are synthesized by another enzyme called primase. An enzyme known as a helicase is required to unwind DNA from a double-strand structure to a single-strand structure to facilitate replication of each strand consistent with the semiconservative model of DNA replication.

Error correction is a property of some, but not all, DNA polymerases. This process corrects mistakes in newly-synthesized DNA. When an incorrect base pair is recognized, DNA polymerase reverses its direction by one base pair of DNA. The 3'->5' exonuclease activity of the enzyme allows the incorrect base pair to be excised (this activity is known as proofreading). Following base excision, the polymerase can re-insert the correct base and replication can continue.

DNA polymerase. (2009, October 19). In Wikipedia, The Free Encyclopedia. Retrieved 03:55, October 31, 2009, from

PDB File

Protein Modification (Golgi)

Elongation Factor EF-TU

EF-Tu (elongation factor thermo unstable) mediates the entry of the aminoacyl tRNA into a free site of the ribosome. EF-Tu functions by binding an aminoacylated, or charged, tRNA molecule in the cytoplasm. This complex transiently enters the ribosome, with the tRNA anticodon domain associating with the mRNA codon in the ribosomal A site. If the codon-anticodon pairing is correct, EF-Tu hydrolyzes GTP into GDP and inorganic phosphate, and changes in conformation to dissociate from the tRNA molecule. The aminoacyl tRNA then fully enters the A site, where its amino acid is brought near the P-site polypeptide and the ribosome catalyzes the covalent transfer of the polypeptide onto the amino acid.

EF-Tu contributes to translational accuracy in three ways. It delays GTP hydrolysis if the tRNA in the ribosome’s A site does not match the mRNA codon, thus preferentially increasing the likelihood for the incorrect tRNA to leave the ribosome. It also adds a second delay (regardless of tRNA matching) after freeing itself from tRNA, before the aminoacyl tRNA fully enters the A site. This delay period is a second opportunity for incorrectly-paired tRNA (and their bound amino acids) to move out of the A site before the incorrect amino acid is irreversibly added to the polypeptide chain. A third mechanism is the less well understood function of EF-Tu to crudely check amino acid-tRNA associations, and reject complexes where the amino acid is not bound to the correct tRNA coding for it.

Exploring the Mitochondria

A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins. The two membranes, however, have different properties. Because of this double-membraned organization, there are five distinct compartments within the mitochondrion. There is the outer mitochondrial membrane, the intermembrane space (the space between the outer and inner membranes), the inner mitochondrial membrane, the cristae space (formed by infoldings of the inner membrane), and the matrix (space within the inner membrane).

Outer membrane

The outer mitochondrial membrane, which encloses the entire organelle, has a protein-to-phospholipid ratio similar to that of the eukaryotic plasma membrane (about 1:1 by weight). It contains large numbers of integral proteins called porins. These porins form channels that allow molecules 5000 Daltons or less in molecular weight to freely diffuse from one side of the membrane to the other. Larger proteins can enter the mitochondrion if a signaling sequence at their N-terminus binds to a large multisubunit protein called translocase of the outer membrane, which then actively moves them across the membrane. Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to certain cell death. The mitochondrial outer membrane can associate with the ER membrane, in a structure called MAM (mitochondria-associated ER-membrane). This is important in ER-mitochondria calcium signaling and involved in the transfer of lipids between the ER and mitochondria.

Intermembrane space

The intermembrane space is basically the space between the outer membrane and the inner membrane. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules such as ions and sugars in the intermembrane space is the same as the cytosol. However, as large proteins must have a specific signaling sequence to be transported across the outer membrane, the protein composition of this space is different than the protein composition of the cytosol. One protein that is localized to the intermembrane space in this way is cytochrome c.

Inner membrane

The inner mitochondrial membrane contains proteins with five types of functions:

1. Those that perform the redox reactions of oxidative phosphorylation
2. ATP synthase, which generates ATP in the matrix
3. Specific transport proteins that regulate metabolite passage into and out of the matrix
4. Protein import machinery.
5. Mitochondria fusion and fission protein

It contains more than 100 different polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion. In addition, the inner membrane is rich in an unusual phospholipid, cardiolipin. This phospholipid was originally discovered in beef hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes. Cardiolipin contains four fatty acids rather than two and may help to make the inner membrane impermeable. Unlike the outer membrane, the inner membrane does not contain porins and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the translocase of the inner membrane (TIM) complex or via Oxa1. In addition, there is a membrane potential across the inner membrane formed by the action of the enzymes of the electron transport chain.

The inner mitochondrial membrane is compartmentalized into numerous cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. These are not simple random folds but rather invaginations of the inner membrane, which can affect overall chemiosmotic function. In typical liver mitochondria, for example, the surface area, including cristae, is about five times that of the outer membrane. Mitochondria of cells that have greater demand for ATP, such as muscle cells, contain more cristae than typical liver mitochondria.These folds are studded with small round bodies known as F1 particles or oxysomes.

The matrix is the space enclosed by the inner membrane. It contains about 2/3 of the total protein in a mitochondrion. The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highly-concentrated mixture of hundreds of enzymes, special mitochondrial ribosomes, tRNA, and several copies of the mitochondrial DNA genome. Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle.

Mitochondria have their own genetic material, and the machinery to manufacture their own RNAs and proteins (see: protein biosynthesis). A published human mitochondrial DNA sequence revealed 16,569 base pairs encoding 37 total genes: 22 tRNA, 2 rRNA, and 13 peptide genes. The 13 mitochondrial peptides in humans are integrated into the inner mitochondrial membrane, along with proteins encoded by genes that reside in the host cell's nucleus.

Zinc Finger Domain Animation

Zinc fingers are small protein domains that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins or small molecules. The name "zinc finger" was coined to describe the hypothesized structure of the repeated unit in Xenopus laevis transcription factor IIIA.


Zinc fingers coordinate zinc ions with a combination of cysteine and histidine residues. They can be classified by the type and order of these zinc coordinating residues (e.g. Cys2His2, Cys4, and Cys6). A more systematic method classifies them into different "fold groups" based on the overall shape of the protein backbone in the folded domain. The most common "fold groups" of zinc fingers are the Cys2His2-like (the "classic zinc finger"), treble clef, and zinc ribbon.


The Cys2His2-like fold group is by far the best characterized class of zinc fingers and are extremely common in mammalian transcription factors. These domains adopt a simple ββα fold and have the amino acid Sequence motif: X2-Cys-X2,4-Cys-X12-His-X3,4,5-His This class of zinc fingers can have a variety of functions such as binding RNA and mediating protein-protein interactions, but is best known for its role in sequence specific DNA-binding proteins such as Zif268. In such proteins, individual zinc finger domains typically occur as tandem repeats with two, three or more fingers comprising the DNA-binding domain of the protein. These tandem arrays can bind in the major groove of DNA and are typically spaced at 3-bp intervals. The α-helix of each domain (often called the "recognition helix") can make sequence specific contacts to DNA bases; residues from a single recognition helix can contact 4 or more bases to yield an overlapping pattern of contacts with adjacent zinc fingers.

Gag knuckle

This fold group is defined by two short β-strands connected by a turn (zinc knuckle) followed by a short helix or loop and resembles the classical Cys2His2 motif with a large portion of the helix and β-hairpin truncated. The best characters members of this family are found in the retroviral nucleocapsid (NC) protein from HIV and other related retroviruses. The gag knuckle zinc finger in the HIV NC protein is the target of a class of drugs known as zinc finger inhibitors.

Treble clef

The treble clef motif consists of a β-hairpin at the N-terminus and an α-helix at the C-terminus that each contribute two ligands for zinc binding, although a loop and a second β-hairpin of varying length and conformation can be present between the N-terminal β-hairpin and the C-terminal α-helix. These fingers are present in a diverse group of proteins that frequently do not share sequence or functional similarity with each other. The best characterized proteins containing treble clef zinc fingers are the [nuclear hormone receptors].


The canonical members of this class contain a binuclear zinc cluster in which two zinc ions are bound by six cysteine residues. These zinc fingers can be found in several transcription factors including the yeast Gal4 protein.

"Zinc finger." Wikipedia, The Free Encyclopedia. 16 Sep 2009, 10:25 UTC. 16 Sep 2009 <>. 

Lysozyme Structure

Lysozymes, also known as muramidase or N-acetylmuramide glycanhydrolase, are a family of enzymes (EC which damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrins. Lysozyme is abundant in a number of secretions, such as tears, saliva, human milk and mucus. It is also present in cytoplasmic granules of the polymorphonuclear neutrophils (PMN). Large amounts of lysozyme can be found in egg white. C-type lysozymes are closely related to alpha-lactalbumin in sequence and structure making them part of the same family.


The enzyme functions by attacking peptidoglycans (found in the cell walls of bacteria, especially Gram-positive bacteria) and hydrolyzing the glycosidic bond that connects N-acetylmuramic acid with the fourth carbon atom of N-acetylglucosamine. It does this by binding to the peptidoglycan molecule in the binding site within the prominent cleft between its two domains. This causes the substrate molecule to adopt a strained conformation similar to that of the transition state[citation needed]. According to Phillips-Mechanism, the lysozyme binds to a hexasaccharide. The lysozyme then distorts the 4th sugar in hexasaccharide (the D ring) into a half-chair conformation. In this stressed state the glycosidic bond is easily broken.

The amino acid side chains glutamic acid 35 (Glu35) and aspartate 52 (Asp52) have been found to be critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, whilst Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule, to give the product of hydrolysis and leaving the enzyme unchanged.

Role in disease
Lysozyme is part of the innate immune system. Children fed infant formula lack lysozyme in their diet and have three times the rate of diarrheal disease. Since lysozyme is a natural form of protection from pathogens like Salmonella, E.coli and Pseudomonas, when it is deficient due to infant formula feeding, can lead to increased incidence of disease.

Whereas the skin is a protective barrier due to its dryness and acidity, the conjunctiva (membrane covering the eye) is instead protected by secreted enzymes, mainly lysozyme and defensin. However, when these protective barriers fail, conjunctivitis results.

PPAR Inhibiors in Cancer Treatment

Poly (ADP-Ribose) Polymerase (PARP) is a protein cells use to repair genetic injuries naturally. But cancer cells also use this protein to repair their own DNA damage. Inhibiting this action allows chemotherapy and radiation to do its job against cancers resulting from genetic mutation.

Alpha Helix

Alpha helix (α-helix) is a right- or left-handed coiled conformation, resembling a spring, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier (i+4 \rightarrow i hydrogen bonding). This secondary structure is also sometimes called a classic Pauling-Corey-Branson alpha helix.


Geometry and hydrogen bonding

The amino acids in an α helix are arranged in a right-handed helical structure where each amino acid corresponds to a 100° turn in the helix (i.e., the helix has 3.6 residues per turn), and a translation of 1.5 Å (= 0.15 nm) along the helical axis. The pitch of the helix (the vertical distance between two points on the helix) is 5.4 Å (= 0.54 nm)which is the product of 1.5 and 3,6. Most importantly, the N-H group of an amino acid forms a hydrogen bond with the C=O group of the amino acid four residues earlier; this repeated i+4 \rightarrow i hydrogen bonding defines an α-helix. Similar structures include the 310 helix (i+3 \rightarrow i hydrogen bonding) and the π-helix (i+5 \rightarrow i hydrogen bonding). These alternative helices are relatively rare, although the 310 helix is often found at the ends of α-helices, "closing" them off. Transient i+2 \rightarrow i helices (sometimes called δ-helices) have also been reported as intermediates in molecular dynamics simulations of α-helical folding.

Residues in α-helices typically adopt backbone (φ, ψ) dihedral angles around (-60°, -45°). More generally, they adopt dihedral angles such that the ψ dihedral angle of one residue and the φ dihedral angle of the next residue sum to roughly -105°. Consequently, α-helical dihedral angles generally fall on a diagonal stripe on the Ramachandran plot (of slope -1), ranging from (-90°, -15°) to (-35°, -70°). For comparison, the sum of the dihedral angles for a 310 helix is roughly -75°, whereas that for the π-helix is roughly -130°. The general formula for the rotation angle Ω per residue of any polypeptide helix with trans isomers is given by the equation.

The α-helix is tightly packed; there is almost no free space within the helix. The amino-acid side chains are on the outside of the helix, and point roughly "downwards" (i.e., towards the N-terminus), like the branches of an evergreen tree (Christmas tree effect). This directionality is sometimes used in preliminary, low-resolution electron-density maps to determine the direction of the protein backbone.


Helices observed in proteins can range from four to over forty residues long, but a typical helix contains about ten amino acids (about three turns). Short polypeptides generally do not exhibit much alpha helical structure in solution, since the entropic cost associated with the folding of the polypeptide chain is not compensated for by a sufficient amount of stabilizing interactions. The backbone hydrogen bonds of α-helices are generally considered slightly weaker than those found in β-sheets, and are readily attacked by the ambient water molecules. However, in more hydrophobic environments such as the plasma membrane, or in the presence of co-solvents such as trifluoroethanol (TFE), or isolated from solvent in the gas phase,[6] oligopeptides readily adopt stable α-helical structure.

Photosystem I

Photosystem I is a proteinaceous transmembrane structure composed of several proteins and embedded with pigment molecules. This structure is located inside chloroplasts and secured within the thylakoid membrane with exposure to the thylakoid lumen on one side and to the chloroplast stroma on the other side. PS I acts as an energy converter for various photosynthetic organisms.

Mechanics of Photosystem I

Light energy in the form of photons is converted into electrons to power the generation of ATP or the reduction of NADP+ to NADPH.[4] Photons are received by an antenna complex of pigment molecules. Antenna molecules become photoexcited and pass the energy as resonance energy (text). The resonance energy is transferred to the reaction center pigment chlorophyll a. The reaction center in turn transfers electrons to a primary electron acceptor and subsequent electron acceptors and carriers. Finally, the electrons reduce NADP+ or help generate ATP. Electrons may be recycled to increase the proton concentration in the thylakoid lumen in a process called cyclic electron flow. In cyclic electron flow electrons are passed from the PS I reaction center and then carried to a cytochromeb6f complex where they help transport protons into the thylakoid lumen thus creating ATP.Plastocyanin may accept electrons from the cytochrome b6f complex and pass them along to the reaction center in the antenna complex beginning the cycle again.

F1 component making ATP

Cyclic Photophosphorylation

In cyclic electron flow, the electron begins in a pigment complex called photosystem I, passes from the primary acceptor to plastoquinone, then to cytochrome b6f (a similar complex to that found in mitochondria), and then to plastocyanin before returning to chlorophyll. This transport chain produces a proton-motive force, pumping H+ ions across the membrane; this produces a concentration gradient which can be used to power ATP synthase during chemiosmosis. This pathway is known as cyclic photophosphorylation, and it does not produce O2, as well as ATP. Unlike non-cyclic photophosphorylation, NADP+ does not accept the electrons, but they are sent back to photosystem I. NADPH is NOT produced in cyclic photophosphorylation. In bacterial photosynthesis, a single photosystem is used, and therefore is involved in cyclic photophosphorylation.

Coenzyme Transporting Electrons to ETC

Chemiosmotic phosphorylation

Chemiosmotic phosphorylation is the third pathway that produces ATP from inorganic phosphate and an ADP molecule. This process is part of oxidative phosphorylation.

The complete breakdown of glucose in the presence of oxygen is called cellular respiration. The last steps of this process occur in mitochondria. The reduced molecules NADH and FADH2 are generated by the Krebs cycle and glycolysis. These molecules pass electrons to an electron transport chain, which uses the energy released to create a proton gradient across the inner mitochondrial membrane. ATP synthase then uses the energy stored in this gradient to make ATP. This process is called oxidative phosphorylation because oxygen is the final electron acceptor and the energy released by reducing oxygen to water is used to phosphorylate ADP and generate ATP.

Non-Cyclic Photophosphorylation

Non-cyclic photo- phosphorylation,cytochrome b6f uses the energy of electrons from PSII to pump protons from the stoma to the lumen. The proton gradient across the thylakoid membrane creates a proton-motive force, used by ATP synthase to form AT

 Non-cyclic photophosphorylation Process

  • Non-cyclic photophosphorylation takes place inside a chloroplast, on or in a thylakoid membrane.
  • A photon of light energy strikes the leaf and hits photosystem 2. The energy will pass from one antenna pigment molecule to another until it reaches a reaction center molecule (p680). The light energy will then energize 2 electrons.
  • The energized electrons now pass to an electron acceptor this creates an electron "hole" within PS2.
  • Water is split inside the thylakoid, providing the electrons to fill the "hole" for photosystem 2. The hydrogen ions, that for the moment are inside the thylakoid, and oxygen which will diffuse out of the chloroplast and the cell.
  • From the electron acceptor the electrons pass to plastoquinone (PQ).
  • From plastoquinone (PQ) the electrons pass on to a complex of cytochromes.
  • As the electrons move from PQ to the cytochrome complex they release enough energy to power the active transport of hydrogen ions from the stroma into the thylakoid space. This generates a large hydrogen ion gradient.
  • From the cytochrome complex the electrons pass on to Photosystem 1 to fill an electron "hole" in PS1.
  • A photon of light energy strikes the leaf and hits photosystem 1. The energy will pass from one antenna pigment molecule to another until it reaches a reaction center molecule (p700). The light energy will then energize 2 electrons.
  • The energized electrons now pass to an electron acceptor this creates the electron "hole" within PS1.
  • From the electron acceptor the electrons pass to ferredoxin (Fd).
  • From ferredoxin (Fd) the electrons and 2 hydrogen ions are used to reduce NADP+ to NADPH + H+. The NADPH + H+ is going to be utlized in the Calvin Cycle (dark reactions).
  • The hydrogen ions that have been pumped into the thylakoid space pass down a concentration gradient through the ATP synthetase complexes. As the ions pass through the synthetase complex their chemiosmotic energy is released.
  • The energy released by the hydrogen ions is used to help convert ADP and a phosphate group into ATP. Some of this ATP is going to be utlized in the Calvin Cycle (dark reactions).

Constitutive Secretion

In constitutive secretion Proteins are continuously secreted from the cell regardless of environmental factors. No external signals are needed to initiate this process. Proteins are packaged in vesicles in the Golgi apparatus and are secreted via exocytosis, all around the cell. Cells that secrete constitutively have many Golgi apparatus scattered throughout the cytoplasm. Fibroblasts, osteoblasts and chondrocytes are some of the many cells that perform constitutive secretion.

Regulated Secretion

Disulfide Bonds

Disulfide bonds play an important role in the folding and stability of some proteins, usually proteins secreted to the extracellular medium. Since most cellular compartments are reducing environments, disulfide bonds are generally unstable in the cytosol with some exceptions as noted below.

Disulfide bonds in proteins are formed between the thiol groups of cysteine residues. The other sulfur-containing amino acid, methionine, cannot form disulfide bonds. A disulfide bond is typically denoted by hyphenating the abbreviations for cysteine, e.g., the "Cys26-Cys84 disulfide bond", or the "26-84 disulfide bond", or most simply as "C26-C84" where the disulfide bond is understood and does not need to be mentioned. The prototype of a protein disulfide bond is the two-amino-acid peptide, cystine, which is composed of two cysteine amino acids joined by a disulfide bond (shown in Figure 2 in its unionized form). The structure of a disulfide bond can be described by its χss dihedral angle between the Cβ − Sγ − Sγ − Cβ atoms, which is usually close to ±90°.

The disulfide bond stabilizes the folded form of a protein in several ways: 1) It holds two portions of the protein together, biasing the protein towards the folded topology. Stated differently, the disulfide bond destabilizes the unfolded form of the protein by lowering its entropy. 2) The disulfide bond may form the nucleus of a hydrophobic core of the folded protein, i.e., local hydrophobic residues may condense around the disulfide bond and onto each other through hydrophobic interactions. 3) Related to #1 and #2, the disulfide bond link two segments of the protein chain, the disulfide bond increases the effective local concentration of protein residues and lowers the effective local concentration of water molecules. Since water molecules attack amide-amide hydrogen bonds and break up secondary structure, a disulfide bond stabilizes secondary structure in its vicinity. For example, researchers have identified several pairs of peptides that are unstructured in isolation, but adopt stable secondary and tertiary structure upon forming a disulfide bond between them.
"Disulfide bond." Wikipedia, The Free Encyclopedia. 20 Jul 2009, 07:46 UTC. 20 Jul 2009 <>.

What is Mad Cow Disease

Bovine spongiform encephalopathy (BSE), commonly known as mad-cow disease (MCD), is a fatal, neurodegenerative disease in cattle, that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 4 years, usually affecting adult cattle at a peak age onset of four to five years, all breeds being equally susceptible.

It is believed by most scientists that the disease may be transmitted to human beings who eat the brain or spinal cord of infected carcasses.[3] In humans, it is known as new variant Creutzfeldt-Jakob disease (vCJD or nvCJD)

Infectious agent
The infectious agent in BSE is believed to be a specific type of misfolded protein called a prion. Those prion proteins carry the disease between individuals and cause deterioration of the brain. BSE is a type of transmissible spongiform encephalopathy (TSE).[10] TSEs can arise in animals that carry an allele which causes previously normal protein molecules to contort by themselves from an alpha helical arrangement to a beta pleated sheet, which is the disease-causing shape for the particular protein. Transmission can occur when healthy animals come in contact with tainted tissues from others with the disease. In the brain these proteins cause native cellular prion protein to deform into the infectious state, which then goes on to deform further prion protein in an exponential cascade. This results in protein aggregates, which then form dense plaque fibers, leading to the microscopic appearance of "holes" in the brain, degeneration of physical and mental abilities, and ultimately death.

"Bovine spongiform encephalopathy." Wikipedia, The Free Encyclopedia. 16 Jul 2009, 20:16 UTC. 16 Jul 2009 <>.

Protein Recycling

Recycling is important not only on a global scale, but also at the cellular level, since key molecules tend to be available in limited numbers. This means a cell needs to have efficient recycling mechanisms.Certain intercellular proteins are needed to respond to specific extracellular signals. This movie covers how such proteins can be stored, recycled and kept available during the periods of time in between the arrival of such extracellular signals.

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Ribosome Ratchet

Comparison of two states of bacterial ribosome, either with fMet - tRNA bound or with elongation factor EF-G bound reveals the significant conformational change that ribosome thought to undergo during each elongation cycle, The Ratchet like rearrangement at interphase between two ribosomal sub unit may help to move the mRNa and tRna through the ribosome during protein synthesis

What is Polyribosome

Polyribosomes (or polysomes) are a cluster of ribosomes, bound to a mRNA molecule, first discovered and characterized by Jonathan Warner, Paul Knopf, and Alex Rich in 1963.Polyribosomes read one strand of mRNA simultaneously, helping to synthesize the same protein at different spots on the mRNA, mRNA being the "messenger" in the process of protein synthesis. They may appear as clusters, linear arrays, or rosettes in routine

Laser Tweezers

An Laser tweezer is a scientific instrument that uses a focused laser beam to provide an attractive or repulsive force (typically on the order of piconewtons), depending on the refractive index mismatch to physically hold and move microscopic dielectric objects. Optical tweezers have been particularly successful in studying a variety of biological systems in recent years.

One of the more common cell-sorting systems makes use of flow cytometry through fluorescent imaging. In this method, a suspension of biologic cells is sorted into two or more containers, based upon specific fluorescent characteristics of each cell during an assisted flow. By using an electrical charge that the cell is "trapped" in, the cells are then sorted based on the fluorescence intensity measurements. The sorting process is undertaken by an electrostatic deflection system that diverts cells into containers based upon their charge.

In the optically-actuated sorting process, the cells are flowed through into an optical landscape i.e. 2D or 3D optical lattices. Without any induced electrical charge, the cells would sort based on their intrinsic refractive index properties and can be re-configurability for dynamic sorting. Mike MacDonald, Gabe Spalding and Kishan Dholakia, Nature 426, 421-424 (2003)[1] made use of diffractive optics and optical elements to create the optical lattice. An automated cell sorter was described at the University of Toronto in 2001, but made use of mechanical parameters as opposed to spatial light modulation

"Optical tweezers." Wikipedia, The Free Encyclopedia. 15 Jul 2009, 07:52 UTC. 15 Jul 2009 <>.

How Depression is caused

Depression is one of the most common psychiatric disorders. Symptoms of depression are often subtle and unrecognized both by patients and physicians. The brain contains a network of interconnected nerve cells called neurons. The junction between the neurons is called the synaptic junction. Chemicals called neuro-transmitters facilitate the transmission of impulses from one neuron to another. The impulse triggers the release of neurotransmitters from one neuron, which cross the synaptic junction and attach themselves to the receptors in adjacent neurons sending the messages through.Later the neuro-transmitter returns to initial neuron the other reuptake channel.One of the causes of depressions believed to be the depletion of neuro transmitter called serotonin and noradrenaline.Antidepressant drugs increase the availability of neuro transmitters at the synaptic junction by blocking the re-uptake channel

Aspartate Transcarbamylase

Aspartate carbamoyltransferase (also known as ATCase or aspartate transcarbamoylase) catalyzes the first step in the pyrimidine biosynthetic pathway.

Enzyme is a multi-subunit protein complex composed of 12 subunits (300 kDa in total). The composition of the subunits is C6R6, forming 2 trimers of catalytic subunits (34 kDa) and 3 dimers of regulatory subunits (17 kDa). The particular arrangement of catalytic and regulatory subunits in this enzyme affords the complex with strongly allosteric behaviour with respect to its substrates. The enzyme is an archetypal example of allosteric modulation of fine control of metabolic enzyme reactions.

ATCase does not follow Michaelis-Menten kinetics, but lies between the high-activity, high-affinity "relaxed" or R and the low-activity, low-affinity "tense" or T states. The binding of substrate to the catalytic subunits result in an equilibrium shift towards the R state, whereas binding of CTP to the regulatory subunits results in an equilibrium shift towards the T state. Binding of ATP to the regulatory subunits results in an equilibrium shift towards the R state.


ATCase is a highly regulated enzyme that catalyses the first committed step in pyrimidine biosynthesis, the condensation of aspartate and carbamyl phosphate to form N-carbamyl-L-aspartate and inorganic phosphate. ATCase controls the rate of pyrimidine biosynthesis by altering its catalytic velocity in response to cellular levels of both pyrimidines and purines. The end product of the pyrimidine pathway, CTP, induces a decrease in catalytic velocity, whereas ATP, the end product of the parallel purine pathway, exerts the opposite effect, stimulating the catalytic activity.

Early studies demonstrated that ATCase consists of two different kinds of polypeptide chains which have different roles. The catalytic subunits catalyze the carbamylation of the amino group of aspartate, but do not have regulatory properties, while the regulatory subunits do not have any catalytic activity, but contain the regulatory sites for effector binding. The ATCase holoenzyme is made of two catalytic trimers that are in contact and held together by three regulatory dimers, so the native form of the enzyme contains six chains of each type, with a total molecular weight of 310 kDa.

Each of the catalytic domains is composed of two structural domains, the aspartate domain that contains most of the residues responsible for binding aspartate, and the carbamoyl phosphate domain, which contains most of the residues that bind to carbamoyl phosphate. Each regulatory domain is also composed of two domains, the allosteric domain that has the binding site for the nucleotide effectors, as well as the zinc domain, consisting of four cysteine residues clustered in its C-terminal region. These residues coordinate a zinc atom that is not involved in any catalytic property, but has been shown to be absolutely essential for the association of regulatory and catalytic subunits.

The three-dimensional arrangement of the catalytic and regulatory subunits involves several ionic and hydrophobic stabilizing contacts between amino acid residues. Each catalytic chain is in contact with three other catalytic chains and two regulatory chains. Each regulatory monomer is in contact with one other regulatory chain and two catalytic chains. In the unliganded enzyme, the two catalytic trimers are also in contact.

Catalytic center
The catalytic site of ATCase is located at the interface between two neighboring catalytic chains in the same trimer and incorporates amino acid side chains from both of these subunits. Insight into the mode of binding of substrates to the catalytic center of ATCase was first made possible by the binding of a bisubstrate analogue, N-(phosphonoacetyl)-L-aspartate (PALA). This compound is a strong inhibitor of ATCase and has a structure that is thought to be very close to that of the transition state of the substrates. Additionally, crystal structures of ATCase bound to carbamoylphosphate and succinate have been obtained. These studies, in addition to investigations using site-directed mutagenesis of specific amino acids have identified several residues that are crucial for catalysis, such as Ser52, Thr53, Arg54, Thr55, Arg105, His134, Gln137, Arg167, Arg229, Glu231, and Ser80 and Lys84 from an adjacent catalytic chain. The active site is a highly positively charged pocket. One of the most critical side chains is from Arg54, which interacts with a terminal oxygen and the anhydride oxygen of carbamoyl phosphate, stabilizing the negative charge of the leaving phosphate group. Arg105, His134, and Thr55 help to increase the electrophilicity of the carbonyl carbon by interacting with the carbonyl oxygen.In general, the rate enhancement of ATCase is achieved by orientation and stabilization of substrates, intermediates, and products rather than by direct involvement of amino acid residues in the catalytic mechanism.

Allosteric site
The allosteric site in the allosteric domain of the R chains of the ATCase complex binds to the nucleotides ATP, CTP and/or UTP. There is one site with high affinity for ATP and CTP and one with 10- to 20- fold lower affinity for these nucleotides in each regulatory dimer.ATP binds predominantly to the high-affinity sites and subsequently activates the enzyme, while UTP and CTP binding leads to inhibition of activity. UTP can bind to the allosteric site, but inhibition of ATCase by UTP is possible only in combination with CTP. With CTP present, UTP binding is enhanced and preferentially directed to the low-affinity sites. Conversely, UTP binding leads to enhanced affinity for CTP at the high-affinity sites and inhibits enzyme activity by up to 95% while CTP binding alone inhibits activity to 50% to 70%. Comparison of the crystal structures of the T and R forms of ATCase show that it swells in size during the allosteric transition, and that the catalytic subunits condense during this process. The two catalytic trimers move apart along the threefold axis by 12 Å, and they rotate about this axis by 5° each, ultimately leading to a reorientation of the regulatory subunits around their twofold axis by 15°. This quaternary structure change is associated with alterations in inter-subunit and inter-domain interactions. The interaction between subunits C1-C4 and R1 is extensively modified during this conversion. In particular, there is large movement of amino acid residues 230-254, known collectively as the 240s loop. These residues are located at the cleft between the carbamoyl phosphate and aspartate domains at the C1-C4 interface. The overall outcome of these structural changes is that the two domains of each catalytic chain come closer together, ensuring a better contact with the substrates or their analogues.

During this structural transition, some side chain-side chain interactions are lost and some others are established. Studies have confirmed that the position of the 240s loop directly affects substrate binding in the corresponding active site.Earlier studies using site-directed mutagenesis of the 240s loop showed that interactions between Asp271 and Tyr240, and between Glu239 of C1 and Tyr165 of C4 would stabilize the T-state, while interactions between Glu239 of C1 and both Lys164 and Tyr165 of C4 would stabilize the R-state.

Located close to the 240s loop and the active site, the loop region encompassing residues 160-166 play a role in both the internal architecture of the enzyme and its regulatory properties. In particular, the residue Asp162 interacts with Gln231 (known to be involved in aspartate binding), and binds the same residues in both the T and R states. A mutant that had this residue mutated to alanine showed a huge reduction in specific activity, a two-fold decrease in the affinity for aspartate, a loss of homotropic cooperativity, and decreased activation by ATP. It was suggested that the change in the overall structure caused by the introduction of this residue affects other residues in the R1-C1, R1-C4 and C1-C4 interfaces, which are involved in the quaternary structure transition.

"Aspartate carbamoyltransferase." Wikipedia, The Free Encyclopedia. 2 Jun 2009, 13:35 UTC. 2 Jun 2009 <>.

Proline Kinks

Integral membrane proteins often contain proline residues in their presumably alpha-helical transmembrane segments. This is in marked contrast to globular proteins, where proline is rarely found inside alpha-helices. Proline residues cause kinks in helices, and, in addition to leaving the i-4 backbone carbonyl without its normal hydrogen bond donor, also sterically prevent the (i-3)-carbonyl-(i + l)-amide backbone hydrogen bond from forming. Here, some structural aspects of proline kinks in transmembrane helices are discussed on the basis of an analysis of Pro-kinked helices in the photosynthetic reaction center and bacteriorhodopsin.


Glucose (Glc), a monosaccharide (or simple sugar) also known as grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate. Glucose is one of the main products of photosynthesis and starts cellular respiration in both prokaryotes (bacteria and archaea) and eukaryotes

Glucose (C6H12O6) contains six carbon atoms, one of which is part of an aldehyde group and is therefore referred to as an aldohexose. In solution, the glucose molecule can exist in an open-chain (acyclic) form and a ring (cyclic) form (in equilibrium). The cyclic form is the result of a covalent bond between the aldehyde C atom and the C-5 hydroxyl group to form a six-membered cyclic hemiacetal. At pH 7 the cyclic form is predominant. In the solid phase, glucose assumes the cyclic form. Because the ring contains five carbon atoms and one oxygen atom (like pyran), the cyclic form of glucose is also referred to as glucopyranose. In this ring, each carbon is linked to a hydroxyl side group with the exception of the fifth atom, which links to a sixth carbon atom outside the ring, forming a CH2OH group. Glucose is commonly available in the form of a white substance or as a solid crystal. It can also be dissolved in water as an aqueous solution.

Lymphocyte Homing

Lymphocyte "homing" process disperses the immunologic repertoire, directs lymphocyte subsets to the specialized microenvironments that control their differentiation and regulate their survival, and targets immune effector cells to sites of antigenic or microbial invasion. Recent advances reveal that the exquisite specificity of lymphocyte homing is determined by combinatorial "decision processes" involving multistep sequential engagement of adhesion and signaling receptors. These homing-related interactions are seamlessly integrated into the overall interaction of the lymphocyte with its environment and participate directly in the control of lymphocyte function, life-span, and population dynamics. In this article a review of the molecular basis of lymphocyte homing is presented, and mechanisms by which homing physiology regulated the homeostasis of immunologic resources are proposed.

Neutrophil Chase

Neutrophils are white blood cells, which hunt and kill bacteria In this video neutrophil can be seen in the mist of red blood cells.Bacteria releases chemo-attractine that is sensed by the neutraphils, the neutrophil becomes polarized and starts chasing the bacteria.The bacteria bounce around by thermal energy move in a random path, avoiding neutrophils. Eventually the neutrophill catches the bacteria and engulfs them by phagocytosis

Cytokine Signaling

Cytokines are a category of signaling molecules that are used extensively in cellular communication. They are proteins, peptides, or glycoproteins. The term cytokine encompasses a large and diverse family of polypeptide regulators that are produced widely throughout the body by cells of diverse embryological origin.

Cytokines typically consists of two chains each having extra-cellular Cytokines binding domain and intracytoplasmic domain, which binds member of family protein tyrosine kinases called Janus kinases or JAK kinase. In the absences of cytokine the two chain do not remain associateded.the cytokine binding to the receptors stabilize the hetero dimer and brings together the JAKs that are bound to the cytoplasmic portions of each chain.

JAKS kinases those are able to phosphoralate cytoplasmic tails of the cytokine receptors.

Signal trasduction and transcription or STAT molecules bind to the phosphorated cytokine receptor chains and phosphorated by JAKS.

The addition of phosphate to the STATs enables them to dimerise and migrate to the nuclues,where the directly activate gene transcription.

Lipids and Membranes

Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The main biological functions of lipids include energy storage, as structural components of cell membranes, and as important signaling molecules.

Membrane is an enclosing or separating amphipathic layer that acts as a barrier within or around a cell. It is, almost invariably, a lipid bilayer, composed of a double layer of lipid (usually phospholipid) molecules and proteins that may constitute close to 50% of membrane content.

Fluorescence Recovery After Photobleaching (FRAP)

Fluorescence recovery after photobleaching (FRAP) denotes an optical technique capable of quantifying the two dimensional lateral diffusion of a molecularity thin film containing fluorescent labeled probes, or to examine single cells. This technique is very useful in biological studies of cell membrane diffusion and protein binding. In addition, surface deposition of a fluorescing phospholipid bilayer (or monolayer) allows the characterization of hydrophilic (or hydrophobic) surfaces in terms of surface structure and free energy. Similar, though less well known, techniques have been developed to investigate the 3-dimensional diffusion and binding of molecules inside the cell; they are also referred to as FRAP.

What is IgG Antibodies

Immunoglobulin G (IgG) is a monomeric immunoglobulin, built of two heavy chains γ and two light chains. Each IgG has two antigen binding sites. It is the most abundant immunoglobulin and is approximately equally distributed in blood and in tissue liquids, constituting 75% of serum immunoglobulins in humans. IgG molecules are synthesised and secreted by plasma B cells.


IgG antibodies are predominately involved in the secondary antibody response, (the main antibody involved in primary response is IgM) which occurs approximately one month following antigen recognition, thus the presence of specific IgG generally corresponds to maturation of the antibody response. Pro-inflammatory cytokines particularly IL-4 and IL-2, have a crucial role in activation of the IgG antibody response.

This is the only isotype that can pass through the human placenta, thereby providing protection to the fetus in utero. Along with IgA secreted in the breast milk, residual IgG absorbed through the placenta provides the neonate with humoral immunity before its own immune system develops.

It can bind to many kinds of pathogens, for example viruses, bacteria, and fungi, and protects the body against them by agglutination and immobilization, complement activation (classical pathway), opsonization for phagocytosis and neutralization of their toxins. It also plays an important role in Antibody-dependent cell-mediated cytotoxicity(ADCC).

IgG is also associated with Type II and Type III Hypersensitivity.

IgG antibodies are large molecules of about 150 kDa composed of 4 peptide chains. It contains 2 identical heavy chains of about 50 kDa and 2 identical light chains of about 25 kDa, thus tetrameric quaternary structure. The two heavy chains are linked to each other and to a light chain each by disulfide bonds. The resulting tetramer has two identical halves which together form the Y-like shape. Each end of the fork contains an identical antigen binding site.


In humans, the three receptors for IgG are:
  • FcγRI (CD64) – 72kDa in size. Expressed on cells of mononuclear phagocyte lineage.
  • FcγRII (CD32) – 40kDa in size. Has 2 forms, alpha (with an ITAM receptor motif) and beta (with an ITIM receptor motif).
  • FcγRIII (CD16) – 50-80kDa in size. Has 2 forms, alpha (a transmembrane protein) and beta (expressed on neutrophils).

Glycosylation is essential for IgG binding to its receptors, regardless of its class

"Immunoglobulin G." Wikipedia, The Free Encyclopedia. 13 Jun 2009, 07:45 UTC. 13 Jun 2009 <>. 

Lecture on Myoglobin and Hemoglobin

Myoglobin is a single-chain globular protein of 153 amino acids, containing a heme (iron-containing porphyrin) prosthetic group in the center around which the remaining apoprotein folds. It has eight alpha helices and a hydrophobic core. It has a molecular weight of 16,700 daltons, and is the primary oxygen-carrying pigment of muscle tissues.

Uptake of Bacteria by Phagocytes

Uptake of bacteria by phagocytes is an active process, which requires triggering of specific receptors on phagocytes.Fc receptor, which binds antibody-coated bacteria, is one of the receptors capable of triggering phagocytosis.
In the case of LPS it is recognize by TLR4 receptor, which is expressed in the surface of dendritic cells.
LPS is transported by a soluble LPS binding protein (LBP) to the surface of dendritic cells, And it’s deposited in cell surface protein (CD14).The presence of LPS is detected by TLR4 though its interaction and recognition of the LPS bound CD14.The signal delivered by TLR initiates maturation of dendritic cell.
Dendritic cell can now migrate to regional lymph nodes and activate required immune response.

Enzymes lecture

Protein Structure Lecture

Innate Recognition of Pathogens

In the initial stage of immune response, the innate immune system recognizes the presence of pathogens and provides the first line of defense.Dendritic cells which are circulating through the tissue has the ability to recognize presence of pathogen associated molecular patterns or PAMPs.PAPMs are conserved features of pathogens such as lipopolysaccharides (LPS) that are components of the cell membrane of all gram-negative bacteria.Dendritic cells have the ability to recognize PAMPs through the expression of family of Toll like receptors (TLRs).

In the case of LPS it is recognize by TLR4 receptor, which is expressed in the surface of dendritic cells.
LPS is transported by a soluble LPS binding protein (LBP) to the surface of dendritic cells, And it’s deposited in cell surface protein (CD14).The presence of LPS is detected by TLR4 though its interaction and recognition of the LPS bound CD14.The signal delivered by TLR initiates maturation of dendritic cell.
Dendritic cell can now migrate to regional lymph nodes and activate required immune response.

Induction of Apoptosis

Apoptosis in T cells and other cells can be activated through cell surface receptors called FAS,Fas are member of TNF receptor family and binds to TNF family member. FasL (FAS ligand) expressed on the surface of other cells, usually activated T cells.
FASL ligands like other TNF family members are a trimmer, and when FAS receptors bind trimmer ligands, three receptors chains are brought together to form a other trimmer.Bringing together the intercellular domains of Fas, which contains adapter molecules called death domains, allows them to bind other intercellular death domains containing protein such as FADD.

A FADD act has an adapter linking FAS to caspase 8;a member of intercellular protease called Caspases.It cleaves at the C terminal side of the aspartic acid residues.Initially Caspase 8 binds as a inactive precursor, but once bound pro-caspase molecule are able activate each other by cleavage and by second cleavage to release the protease domain from the complex proteins assembled around the Fas receptors.
Caspase 8 proteolytic domain activates other pro-caspases, which can in turn activates other pro-caspases in a proteolytc cascade.At the end of the cascade is a important effector caspase called caspase 3,which cleaves the protein called I-CAD the inhibitor of caspase activated DNA.By cleaving I-CAD inhibitor, the caspase3 releases active DNA, which is able to migrate to nucleus.In the nucleus the caspase activated DNA degrades chromatin, cutting the DNA into small pieces and ultimately killing the cell