Interplay between hydrophobic cluster and loop propensity in beta-hairpin formation.
Autonomously folding beta-hairpins have recently emerged as powerful tools for elucidating the origins of antiparallel beta-sheet folding preferences. Analysis of such model systems has suggested four potential sources of beta-sheet stability: (1) the conformational propensity of the loop segment that connects adjacent strands; (2) favorable contacts between side-chains on adjacent strands; (3) interstrand hydrogen bonds; and (4) the intrinsic beta-sheet propensities of the strand residues. We describe the design and analysis of a series of isomeric 20 residue peptides in which factors (1)-(4) are identical. Differences in beta-hairpin formation within this series demonstrate that these four factors, individually, are not sufficient to explain beta-sheet stability. In agreement with the prediction of a simple statistical mechanical model for beta-hairpin formation, our results show that the separation between the loop segment and an interstrand cluster of hydrophobic side-chains strongly influences beta-hairpin size and stability, with a smaller separation leading to greater stability.
Espinosa
J F
JF
Department of Chemistry, University of Wisconsin, Madison 53706, USA.
Muñoz
V
V
Gellman
S H
SH
D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D010455:Peptides