Many residues in cytochrome c populate alternative states under equilibrium conditions
A curved temperature dependence of an amide proton NMR chemical shift indicates that it explores discrete alternative conformations at least 1% of the time; that is, it accesses conformations that lie within 5 kcal/mol−1 of the ground state. The simulations presented show how curvature varies with t...
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Published in | Proteins, structure, function, and bioinformatics Vol. 53; no. 3; pp. 731 - 739 |
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Main Author | |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
15.11.2003
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Subjects | |
Online Access | Get full text |
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Summary: | A curved temperature dependence of an amide proton NMR chemical shift indicates that it explores discrete alternative conformations at least 1% of the time; that is, it accesses conformations that lie within 5 kcal/mol−1 of the ground state. The simulations presented show how curvature varies with the nature of the alternative state, and are compared to experimental results. From studies in different denaturant concentrations, it is concluded that at least 25% of residues in reduced horse cytochrome c, covering most of the protein, with the exception of the center of the N‐ and C‐terminal helices, visit alternative states under equilibrium conditions. The conformational ensemble of the protein therefore has high structural entropy. The density of alternative states is particularly high near the heme ligand Met80, which is of interest because both redox change and the first identified stage in unfolding are associated with change in Met80 ligation. By combining theoretical and experimental approaches, it is concluded that the alternative states each comprise approximately five residues, have in general less structure than the native state, and are accessed independently. They are therefore locally unfolded structures. The locations of the alternative states match what is known of the global unfolding pathway of cytochrome c, suggesting that they may determine the pathway. Proteins 2003;53:000–000. © 2003 Wiley‐Liss, Inc. |
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Bibliography: | equipment grant from Wellcome Trust istex:EF0BF023F34286B4B3B160B28F205C80C2DA4ED8 ArticleID:PROT10464 ark:/67375/WNG-BMFR0CTP-N MPW is a member of the BBSRC‐funded North of England Structural Biology Centre (NESBIC). ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0887-3585 1097-0134 |
DOI: | 10.1002/prot.10464 |