The solution structure of the isolated fragments 1-20 (beta-hairpin), 21-40 (alpha-helix) and 41-56 (beta-hairpin), corresponding to all the secondary structure elements of the protein G B1 domain, have been studied by circular dichroism and nuclear magnetic resonance techniques. In the protein G B1-(1-20) fragment turn-like folded structures were detected in water though low populated. In the presence of 30% aqueous trifluoroethanol there is a complex conformational behaviour in which a helical structure at the N-terminal half is formed in equilibrium with random and native-like beta-hairpin structures. The peptide corresponding to the alpha-helix is predominantly unstructured in water, while in 30% trifluoroethanol it highly populates a native alpha-helical conformation, including a (i,i + 5) interaction between hydrophobic residues at its C-terminus. The third peptide was previously reported to form a monomeric native beta-hairpin structure in water . We show in this work that the beta-hairpin structure is further stabilized in 30% trifluoroethanol and destabilised in the presence of 6 M urea, though some folded structure persists even in these highly denaturing conditions. The conformational properties of these peptides suggests that the second beta-hairpin could be an important folding initiation site on which the rest of the chain folds. Reconstitution experiments failed to show evidence of interaction between the peptides. Algorithms designed to predict the helical and extended conformations of peptides in aqueous solution successfully describe the complicated behaviour of these peptides. Comparison of the predicted and the experimental results with those for a structurally related protein, ubiquitin, shows very strong similarities, the main difference being the switch of the most stable beta-hairpin from the N-terminus in ubiquitin to the C-terminus in protein G.
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