Solution Structure, Dynamics, and Thermodynamics of the Native State Ensemble of the Sem-5 C-Terminal SH3 Domain
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- 作者：Josephine C. Ferreon ; David E. Volk ; Bruce A. Luxon ; David G. Gorenstein ; and Vincent J. Hilser
- 刊名：Biochemistry
- 出版年：2003
- 出版时间：May 20, 2003
- 年：2003
- 卷：42
- 期：19
- 页码：5582 - 5591
- 全文大小：319K
- 年卷期：v.42,no.19(May 20, 2003)
- ISSN：1520-4995
文摘
Although the high-resolution structure of a protein may provide significant insight into whichregions are important for function, it is well-known that proteins undergo significant conformationalfluctuations, even under native conditions. This suggests that the static structure alone may not providesufficient information for elucidation of the thermodynamic determinants of biological function and thatan accurate molecular-level description of function requires knowledge of the nature and energetics ofthe conformational states that constitute the native state ensemble. Here the native state ensemble of theC-terminal src homology domain-3 (C-SH3) from Caenorhabditis elegans Sem-5 has been studied usinga variety of high-resolution biophysical techniques. In addition to determining the first solution structureof the unliganded protein, we have performed 15N relaxation and native state hydrogen-deuterium exchange.It is observed that the regions of greatest structural variabilility also show low protection and orderparameters, suggesting a higher degree of conformational diversity. These flexible regions also coincidewith those regions of Sem-5 that have been predicted by the COREX algorithm to be unfolded in manyof the most probable conformational states within the native state ensemble. The implications of thisagreement and the potential role of conformational heterogeneity of the observed biophysical propertiesare discussed.