蛋白质集合的统计热力学:中介功能和进化。

IF 10.4 1区 生物学 Q1 BIOPHYSICS
Vincent J Hilser, James O Wrabl, Charles E F Millard, Anna Schmitz, Sarah J Brantley, Marie Pearce, Joe Rehfus, Miranda M Russo, Keila Voortman-Sheetz
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引用次数: 0

摘要

对介导蛋白质功能的天然状态构象波动的日益重视,要求对蛋白质进化和适应进行批判性的重新评估。如果蛋白质是集合体,自然是只选择基态结构,还是功能态之间的构象平衡也是守恒的?如果有,它的机制是什么?如何测量?为了解决这些基本问题,我们回顾了我们对蛋白质天然状态集合中局部展开波动的作用的研究。通过对腺苷酸激酶的研究,我们描述了这些无处不在的波动的功能重要性。然后,我们总结了热力学组织原理的阐明,最终在蛋白质能量学进化守恒的定量探测中达到高潮。最后,我们表明这些原则是预测序列相容性的多重折叠,提供了一个独特的热力学角度对变质蛋白。这些研究表明,局部未折叠的集合是一种新兴的、重要的蛋白质进化机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Statistical Thermodynamics of the Protein Ensemble: Mediating Function and Evolution.

The growing appreciation of native state conformational fluctuations mediating protein function calls for critical reevaluation of protein evolution and adaptation. If proteins are ensembles, does nature select solely for ground state structure, or are conformational equilibria between functional states also conserved? If so, what is the mechanism and how can it be measured? Addressing these fundamental questions, we review our investigation into the role of local unfolding fluctuations in the native state ensembles of proteins. We describe the functional importance of these ubiquitous fluctuations, as revealed through studies of adenylate kinase. We then summarize elucidation of thermodynamic organizing principles, which culminate in a quantitative probe for evolutionary conservation of protein energetics. Finally, we show that these principles are predictive of sequence compatibility for multiple folds, providing a unique thermodynamic perspective on metamorphic proteins. These research areas demonstrate that the locally unfolded ensemble is an emerging, important mechanism of protein evolution.

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来源期刊
Annual Review of Biophysics
Annual Review of Biophysics 生物-生物物理
CiteScore
21.00
自引率
0.00%
发文量
25
期刊介绍: The Annual Review of Biophysics, in publication since 1972, covers significant developments in the field of biophysics, including macromolecular structure, function and dynamics, theoretical and computational biophysics, molecular biophysics of the cell, physical systems biology, membrane biophysics, biotechnology, nanotechnology, and emerging techniques.
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