About the structural role of disulfide bridges in serum albumins: Evidence from protein simulated unfolding

Authors

  • Guillaume Paris,

    1. Laboratoire Chrono Environnement UMR CNRS 6249, Faculté des Sciences et Techniques, La Bouloie, Université de Franche-Comté, 25030 Besançon cedex, France
    Search for more papers by this author
  • Sebastian Kraszewski,

    1. Laboratoire de Nanomédecine, Imagerie et Thérapeutique EA 4662, Faculté des Sciences et Techniques, La Bouloie, Université de Franche-Comté, CHU Besançon, 25030 Besançon cedex, France
    Search for more papers by this author
  • Christophe Ramseyer,

    1. Laboratoire de Nanomédecine, Imagerie et Thérapeutique EA 4662, Faculté des Sciences et Techniques, La Bouloie, Université de Franche-Comté, CHU Besançon, 25030 Besançon cedex, France
    Search for more papers by this author
  • Mironel Enescu

    Corresponding author
    1. Laboratoire Chrono Environnement UMR CNRS 6249, Faculté des Sciences et Techniques, La Bouloie, Université de Franche-Comté, 25030 Besançon cedex, France
    • Laboratoire Chrono Environnement UMR CNRS 6249, Faculté des Sciences et Techniques, La Bouloie, Université de Franche-Comté, 25030 Besançon cedex, France
    Search for more papers by this author

  • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

Abstract

The role of the 17 disulfide (S[BOND]S) bridges in preserving the native conformation of human serum albumin (HSA) is investigated by performing classical molecular dynamics (MD) simulations on protein structures with intact and, respectively, reduced S[BOND]S bridges. The thermal unfolding simulations predict a clear destabilization of the protein secondary structure upon reduction of the S[BOND]S bridges as well as a significant distortion of the tertiary structure that is revealed by the changes in the protein native contacts fraction. The effect of the S[BOND]S bridges reduction on the protein compactness was tested by calculating Gibbs free energy profiles with respect to the protein gyration radius. The theoretical results obtained using the OPLS-AA and the AMBER ff03 force fields are in agreement with the available experimental data. Beyond the validation of the simulation method, the results here reported provide new insights into the mechanism of the protein reductive/oxidative unfolding/folding processes. It is predicted that in the native conformation of the protein, the thiol ([BOND]SH) groups belonging to the same reduced S[BOND]S bridge are located in potential wells that maintain them in contact. The [BOND]SH pairs can be dispatched by specific conformational transitions of the peptide chain located in the neighborhood of the cysteine residues. © 2012 Wiley Periodicals, Inc. Biopolymers 97:889–898, 2012.

Ancillary