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 <http://en.wikipedia.org/w/index.php?title=Disulfide_bond&oldid=303092230>.