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Residual structure in a peptide fragment of the outer membrane protein X under denaturing conditions: a molecular dynamics study

Kräutler, Vincent ; Hiller, Sebastian ; Hünenberger, Philippe

In: European Biophysics Journal, 2010, vol. 39, no. 10, p. 1421-1432

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    Titel
    • Residual structure in a peptide fragment of the outer membrane protein X under denaturing conditions: a molecular dynamics study
    Autor
    • Kräutler, Vincent. Laboratory of Physical Chemistry, ETH Zürich, 8093, Zürich, Switzerland
    • Hiller, Sebastian. Laboratory of Physical Chemistry, ETH Zürich, 8093, Zürich, Switzerland
    • Hünenberger, Philippe. Laboratory of Physical Chemistry, ETH Zürich, 8093, Zürich, Switzerland
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • European Biophysics Journal, 2010, vol. 39, no. 10, p. 1421-1432. Springer-Verlag
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:318636
    Summary
    The Escherichia coli outer membrane protein X (OmpX) contains two polypeptide segments that present nonrandom residual structure in 8M aqueous urea, whereas the remainder of the protein is in a flexibly disordered conformation (Tafer et al. in Biochemistry 43:860-869, 2004). In the present study, the results of two long-timescale (0.4μs) unrestrained explicit-solvent molecular dynamics (MD) simulations of a tetradecapeptide representative of one of these two segments in 8M aqueous urea are reported and analyzed. The two simulations were initiated either from the conformation of the corresponding segment in an NMR model structure of the unfolded protein or from an entirely extended configuration. The sampled conformational ensembles agree qualitatively with the experimentally observed NOEs, but not quantitatively, suggesting that a number of relevant configurations were not visited on the 2×0.4μs timescale. Major conformational transitions occur on the 0.1μs timescale, and the ensembles corresponding to the two independent simulations overlap only to a limited extent. However, both simulations show in multiple events the reversible formation and disruption of α-helical secondary structure (characteristic of the urea-denatured state) and β-turn secondary structure (characteristic of the native state). Events of helix formation are correlated with the appearance of hydrogen bonds between two side chains (Asp75-Ser78) and of a persistent hydrophobic contact (Trp76-Tyr80). They also evidence a peculiar helix stabilization and N-terminal capping role for a negatively charged residue (Asp75). These features are in good qualitative agreement with the NMR model for the structured state of the corresponding segment in the urea-denatured protein. The analysis of the simulations provides a detailed picture of the structural and dynamic features of the considered peptide at atomic resolution that is of high relevance in the understanding of the OmpX folding process