β-Hairpin formation in aqueous solution and in the presence of trifluoroethanol: A 1H and 13C nuclear magnetic resonance conformational study of designed peptides

Abstract

In order to check our current knowledge on the principles involved in β-hairpin formation, we have modified the sequence of a 3:5 β-hairpin forming peptide with two different purposes, first to increase the stability of the formed 3:5 β-hairpin, and second to convert the 3:5 β-hairpin into a 2:2 β-hairpin. The conformational behavior of the designed peptides was investigated in aqueous solution and in 30% trifluoroethanol (TFE) by analysis of the following nuclear magnetic resonance (NMR) parameters: nuclear Overhauser effect (NOE) data, and C_αH, ¹³C_α, and ¹³C_β conformational shifts. From the differences in the ability to adopt β-hairpin structures in these peptides, we have arrived to the following conclusions: (i) β-Hairpin population increases with the statistical propensity of residues to occupy each turn position. (ii) The loop length, and in turn, the β-hairpin type, can be modified as a function of the type of turn favored by the loop sequence. These two conclusions reinforce previous results about the importance of β-turn sequence in β-hairpin folding. (iii) Side-chain packing on each face of the β-sheet may play a major role in β-hairpin stability; hence simplified analysis in terms of isolated pair interactions and intrinsic β-sheet propensities is insufficient. (iv) Contributions to β-hairpin stability of turn and strand sequences are not completely independent. (v) The burial of hydrophobic surface upon β-hairpin formation that, in turn, depends on side-chain packing also contributes to β-hairpin stability. (vi) As previously observed, TFE stabilizes β-hairpin structures, but the extent of the contribution of different factors to β-hairpin formation is sometimes different in aqueous solution and in 30% TFE. © 2005 Wiley Periodicals, Inc. Biopolymers 79: 150–162, 2005

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