Protein folding, protein collapse, and tanford's transfer model: lessons from single-molecule FRET.
Protein folding, protein collapse, and tanford's transfer model: lessons from single-molecule FRET.
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DOI：
10.1021/ja808305u
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发表时间：
2009-03-04
影响因子：
15
通讯作者：
Haran G
中科院分区：
文献类型：
--
作者：
Ziv G;Haran G
近年来，蛋白质变性状态在其折叠反应中的重要作用越来越受到关注。单分子FRET（smFRET）实验表明，随着化学变性剂浓度的降低，变性态经历了一个连续的塌缩（或从线团到小球）转变，这表明变性态的构象熵是折叠自由能的重要组成部分。这样的观察质疑经典Tanford转移模型的有效性，该模型表明折叠自由能可以仅仅基于折叠状态和固定的未折叠状态之间的氨基酸溶剂化的差异来理解。另一种转移模型是从一系列已发表的smFRET数据的聚合物理论分析中获得的。分析表明，变性态坍塌的自由能与变性剂浓度呈线性关系，是热力学和熵贡献相互作用的结果。令人惊讶的是，崩塌自由能的斜率与折叠自由能的斜率非常一致。从两个非常不同的测量获得的值的一致性表明，它是在变性状态下介导的变性剂对折叠的影响的崩溃过渡。因此，折叠的能量学由变性状态下的溶剂化和构象熵的竞争决定。
The essential and non-trivial role of the denatured state of proteins in their folding reaction is being increasingly scrutinized in recent years. Single molecule FRET (smFRET) experiments show that the denatured state undergoes a continuous collapse (or coil-to-globule) transition as the concentration of a chemical denaturant is decreased, suggesting that conformational entropy of the denatured state is an important part of the free energy of folding. Such observations question the validity of the classical Tanford transfer model, which suggests that the folding free energy can be understood solely based on the difference in amino acid solvation between the folded state and a fixed unfolded state. An alternative to the transfer model is obtained here from a polymer theoretical analysis of a series of published smFRET data. The analysis shows that the free energy of denatured-state collapse has a linear dependence on denaturant concentration, an outcome of the interplay between enthalpic and entropic contributions. Surprisingly, the slope of the free energy of collapse agrees very well with the respective slope of the free energy of folding. This conformity of values obtained from two very different measurements shows that it is the collapse transition in the denatured state which mediates the effect of denaturants on folding. The energetics of folding are thus governed by the competition of solvation and conformational entropy in the denatured state.
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DOI：
10.1073/pnas.0508584102
发表时间：
2005-11-29
影响因子：
11.1
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发表时间：
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影响因子：
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DOI：
10.1073/pnas.0611503104
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影响因子：
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