Protein Science, Vol 6, Issue 12 2548-2560, Copyright © 1997 by Cold Spring Harbor Laboratory Press

ARTICLE

Cross-strand side-chain interactions versus turn conformation in {beta}-hairpins

E. D. ALBA, M. RICO and M. A. JIMENEZ
Instituto de Estructura de la Materia, Consejo Superior de Investigaciones Cientificas, Serrano 119, 28006-Madrid, Spain

A series of designed peptides has been analyzed by (1)H-NMR spectroscopy in order to investigate the influence of cross-strand side-chain interactions in {beta}-hairpin formation. The peptides differ in the N-terminal residues of a previously designed linear decapeptide that folds in aqueous solution into two interconverting {beta}-hairpin conformations, one with a type I turn ({beta}-hairpin 4:4) and the other with a type I + G1 {beta}-bulge turn ({beta}-hairpin 3:5). Analysis of the conformational behavior of the peptides studied here demonstrates three favorable and two unfavorable cross-strand side-chain interactions for {beta}-hairpin formation. These results are in agreement with statistical data on side-chain interactions in protein {beta}-sheets. All the peptides in this study form significant populations of the {beta}-hairpin 3:5, but only some of them also adopt the {beta}-hairpin 4:4. The formation of {beta}-hairpin 4:4 requires the presence of at least two favorable cross-strand interactions, whereas {beta}-hairpin 3:5 seems to be less susceptible to side-chain interactions. A protein database analysis of {beta}-hairpins 3:5 and {beta}-hairpins 4:4 indicates that the former occur more frequently than the latter. In both peptides and proteins, {beta}-hairpins 3:5 have a larger right-handed twist than {beta}-hairpins 4:4, so that a factor contributing to the higher stability of {beta}-hairpin 3:5 relative to {beta}-hairpin 4:4 is due to an appropriate backbone conformation of the type I + G1 {beta}-bulge turn toward the right-handed twist usually observed in protein {beta}-sheets. In contrast, as suggested previously, backbone geometry of the type I turn is not adequate for the right-handed twist. Because analysis of buried hydrophobic surface areas on protein {beta}-hairpins reveals that {beta}-hairpins 3:5 bury more hydrophobic surface area than {beta}-hairpins 4:4, we suggest that the right-handed twist observed in {beta}-hairpin 3:5 allows a better packing of side chains and that this may also contribute to its higher intrinsic stability.
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