Mutational analysis of m-values as a strategy to identify cold-resistant substructures of the protein ensemble
Article first published online: 31 OCT 2011
Copyright © 2011 Wiley Periodicals, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 80, Issue 1, pages 184–193, January 2012
How to Cite
Campbell, J. C. and Whitten, S. T. (2012), Mutational analysis of m-values as a strategy to identify cold-resistant substructures of the protein ensemble. Proteins, 80: 184–193. doi: 10.1002/prot.23178
- Issue published online: 13 DEC 2011
- Article first published online: 31 OCT 2011
- Accepted manuscript online: 14 SEP 2011 04:03PM EST
- Manuscript Accepted: 24 AUG 2011
- Manuscript Revised: 19 AUG 2011
- Manuscript Received: 23 MAY 2011
Characterizing the native ensemble of protein is an important yet difficult objective of structural biology. The structural dynamics of protein macromolecules play key roles in biological function, but the short lifetimes and low population of near-native states of the protein ensemble limit their ability to be studied directly. In part to address such issues, it was shown recently that the cooperative substructures that populate a protein ensemble could be ascertained by NMR methods performed at very cold temperatures. What is presented here is an argument that these same substructures can also be determined by denaturant-induced unfolding studies performed on protein at room temperature. Data supporting this argument are given for Staphylococcal nuclease, chymotrypsin inhibitor 2, and ubiquitin. The observation of an agreement between the thermodynamics of the protein ensemble simulated under very cold temperatures to the apparent sensitivity of the ensemble to chemical denaturants at room temperature also suggests that the overall structural–thermodynamic character of an ensemble is surprisingly robust and preserved even in the presence of strong denaturing conditions. Proteins 2012; © 2011 Wiley Periodicals, Inc.