15N backbone dynamics of the S-peptide from ribonuclease A in its free and S-protein bound forms: Toward a site-specific analysis of entropy changes upon folding

Andrei T. Alexandrescu, Klara Rathgeb-Szabo, Klaus Rumpel, Wolfgang Jahnke, Therese Schulthess, Richard A. Kammerer

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Backbone 15N relaxation parameters (R1, R2, 1H-15N NOE) have been measured for a 22-residue recombinant variant of the S-peptide in its free and S-protein bound forms. NMR relaxation data were analyzed using the 'model-free' approach (Lipari and Szabo, 1982). Order parameters obtained from 'model-free' simulations were used to calculate 1H-15N bond vector entropies using a recently described method (Yang and Kay, 1996), in which the form of the probability density function for bond vector fluctuations is derived from a diffusion-in-a-cone motional model. The average change in 1H- 15N bond vector entropies for residues T3-S15, which become ordered upon binding of the S-peptide to the S-protein, is -12.6 ± 1.4 J/mol · residue · K. 15N relaxation data suggest a gradient of decreasing entropy values moving from the termini toward the center of the free peptide. The difference between the entropies of the terminal and central residues is about -12 J/mol · residue · K, a value comparable to that of the average entropy change per residue upon complex formation. Similar entropy gradients are evident in NMR relaxation studies of other denatured proteins. Taken together, these observations suggest denatured proteins may contain entropic contributions from non-local interactions. Consequently, calculations that model the entropy of a residue in a denatured protein as that of a residue in a di- or tri-peptide, might over-estimate the magnitude of entropy changes upon folding.
    Original languageEnglish
    Pages (from-to)389-402
    Number of pages13
    JournalProtein science
    Volume7
    Issue number2
    Publication statusPublished - Feb 1998

    Keywords

    • Backbone entropy
    • Conformational entropy
    • End effects
    • NMR relaxation
    • Order parameter
    • Protein folding
    • Protein stability
    • Random coil

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