Size and Sequence and the Volume Change of Protein Folding
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- 作者：Jean-Baptiste Rouget ; Tural Aksel ; Julien Roche ; Jean-Louis Saldana ; Angel E. Garcia ; Doug Barrick ; Catherine A. Royer
- 刊名：Journal of the American Chemical Society
- 出版年：2011
- 出版时间：April 20, 2011
- 年：2011
- 卷：133
- 期：15
- 页码：6020-6027
- 全文大小：996K
- 年卷期：v.133,no.15(April 20, 2011)
- ISSN：1520-5126
文摘
The application of hydrostatic pressure generally leads to protein unfolding, implying, in accordance with Le Chatelier鈥檚 principle, that the unfolded state has a smaller molar volume than the folded state. However, the origin of the volume change upon unfolding, 螖Vu, has yet to be determined. We have examined systematically the effects of protein size and sequence on the value of 螖Vu using as a model system a series of deletion variants of the ankyrin repeat domain of the Notch receptor. The results provide strong evidence in support of the notion that the major contributing factor to pressure effects on proteins is their imperfect internal packing in the folded state. These packing defects appear to be specifically localized in the 3D structure, in contrast to the uniformly distributed effects of temperature and denaturants that depend upon hydration of exposed surface area upon unfolding. Given its local nature, the extent to which pressure globally affects protein structure can inform on the degree of cooperativity and long-range coupling intrinsic to the folded state. We also show that the energetics of the protein鈥檚 conformations can significantly modulate their volumetric properties, providing further insight into protein stability.