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Modulation of intrinsic φ,ψ propensities of amino acids by neighbouring residues in the coil regions of protein structures: NMR analysis and dissection of a β-hairpin peptide 1 1Edited by P. E. Wright

1998; Elsevier BV; Volume: 284; Issue: 5 Linguagem: Inglês

10.1006/jmbi.1998.2264

1089-8638

Sam Griffiths‐Jones, Gary J. Sharman, Allister J. Maynard, Mark S. Searle,

Enzyme Structure and Function

Analysis of residues in coil regions of protein structures presents a novel approach to deconvoluting the various competing factors which determine the intrinsic φ,ψ propensities of amino acids free from the regular interactions associated with β-strands and α-helices. We have considered the role of context on φ,ψ preferences by examining the effects of neighbouring residues in modulating coil propensities within a data base of 512 high-resolution, low-homology structures. In the general case, when flanking residues are β-branched or aromatic (Val, Ile, Tyr and Phe) the β-propensity (Pβ) increases significantly, largely due to steric effects between flanking residues. More subtle residue-specific effects are apparant when Pβ values are examined in detail, showing "random coil" conformations to be highly sequence-dependent. The effects of flanking residues on φ distributions have been used to calculate context-dependent average 3JNH-Hα coupling constants. We have examined these findings in the context of the folding of a model 16-residue β-hairpin peptide, "mutant" hairpin (VSI→KSK sequence change) and the isolated C-terminal β-strand fragments of both hairpins. We find a better correlation between 3JNH-Hα values derived from the data base model and those determined experimentally when context-dependent φ distributions are considered. The individual C-terminal β-strand sequences (GKKITVSIversus GKKITKSK) of the two hairpins are predisposed to different extents to formation of an extended β-like conformation. Conformational "predisposition" in this context may contribute significantly to β-hairpin stability.