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

Samuel R. Griffiths-Jones, Gary J. Sharman, Allister J. Maynard, Mark S. Searle

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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 (P(β)) increases significantly, largely due to steric effects between flanking residues. More subtle residue-specific effects are apparant when P(β) 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 3J(NH-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 3J(NH-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 (GKKITVSI versus 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.
    Original languageEnglish
    Pages (from-to)1597-1609
    Number of pages12
    JournalJournal of molecular biology
    Volume284
    Issue number5
    DOIs
    Publication statusPublished - 18 Dec 1998

    Keywords

    • β-hairpin
    • φ,ψ propensities
    • NMR coupling constants
    • Protein data base
    • Random coil

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