Protein folding is slaved to solvent motions
Protein folding is slaved to solvent motions
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DOI：
10.1073/pnas.0607168103
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发表时间：
2006-10-17
影响因子：
11.1
通讯作者：
McMahon, B. H.
中科院分区：
文献类型：
--
作者：
Frauenfelder, H.;Fenimore, P. W.;McMahon, B. H.
蛋白质是生命系统的主力，由氨基酸链构成，氨基酸链根据遗传密码的指令在细胞中合成，然后折叠成工作蛋白质。折叠的时间从微秒到几小时不等。到底是什么控制了折叠率，这一点引起了激烈的争论。我们在这里假设折叠与本体溶剂中的α波动具有相同的温度依赖性，但速度慢得多。我们称这种行为为奴役。在折叠蛋白质中观察到了奴役现象：大规模蛋白质运动遵循速率系数 k(alpha) 的溶剂波动，但速度可能会慢很多。之所以会出现减速，是因为大规模运动以许多小步进行，每个小步都由 k(alpha) 决定。如果折叠蛋白质的构象运动是从动的，那么折叠过程中的运动就更不用说了。展开的蛋白质在构象空间中进行布朗运动直至折叠结构，每一步都由 k(alpha) 控制。由于未折叠蛋白质中构象亚状态的数量非常多，因此折叠率系数 k(f) 远小于 k(alpha)。奴隶模型意味着折叠的活化焓由溶剂决定，而步骤数 n(f) = k(alpha)/k(f) 则由未折叠蛋白质和溶剂中可接近的亚态数量控制。然而，蛋白质不仅会经历α波动，还会经历β波动。这些额外的波动是局部蛋白质运动，基本上独立于本体溶剂波动，并且可能与折叠的后期阶段相关。
Proteins, the workhorses of living systems, are constructed from chains of amino acids, which are synthesized in the cell based on the instructions of the genetic code and then folded into working proteins. The time for folding varies from microseconds to hours. What controls the folding rate is hotly debated. We postulate here that folding has the same temperature dependence as the a-fluctuations in the bulk solvent but is much slower. We call this behavior slaving. Slaving has been observed in folded proteins: Large-scale protein motions follow the solvent fluctuations with rate coefficient k(alpha) but can be slower by a large factor. Slowing occurs because large-scale motions proceed in many small steps, each determined by k(alpha). if conformational motions of folded proteins are slaved, so a fortiori must be the motions during folding. The unfolded protein makes a Brownian walk in the conformational space to the folded structure, with each step controlled by k(alpha). Because the number of conformational substates in the unfolded protein is extremely large, the folding rate coefficient, k(f), is much smaller than k(alpha). The slaving model implies that the activation enthalpy of folding is dominated by the solvent, whereas the number of steps n(f) = k(alpha)/k(f) is controlled by the number of accessible substates in the unfolded protein and the solvent. Proteins, however, undergo not only alpha- but also beta-fluctuations. These additional fluctuations are local protein motions that are essentially independent of the bulk solvent fluctuations and may be relevant at late stages of folding.