The folding cooperativity of a protein is controlled by its chain topology.
The folding cooperativity of a protein is controlled by its chain topology.
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作者：
蛋白质的三维结构通常显示出由离散的结构区域或结构域组成的模块化架构。这些区域之间的合作通信对于催化、调节和有效折叠是重要的;缺乏偶联已经涉及原纤维的形成和其他错误折叠病理。然而，蛋白质的不同结构区域如何通信并有助于蛋白质的整体能量学和折叠，仍然知之甚少。在这里，我们使用单分子光镊的方法来诱导T4溶菌酶的特定区域的选择性展开，并监测对其他区域的影响，而不是直接作用于力。我们研究了蛋白质的拓扑结构（结构元素沿序列的沿着顺序）如何影响其结构域之间的耦合和折叠协同性。为了探索不直接受力区域的状态，我们利用克鲁克斯涨落定理确定了力学展开过程中自由能的变化。我们拉上拓扑变体（环状排列），发现多肽链的拓扑结构决定了结构域之间的折叠协同性，从而决定了折叠/展开景观的哪些部分被探索。我们推测，蛋白质可能已经进化到选择某些拓扑结构，增加区域之间的耦合，以避免导致动力学捕获和错误折叠的景观区域。
The three-dimensional structures of proteins often show a modular architecture comprised of discrete structural regions or domains. Cooperative communication between these regions is important for catalysis, regulation and efficient folding; lack of coupling has been implicated in the formation of fibrils and other misfolding pathologies. How different structural regions of a protein communicate and contribute to a protein’s overall energetics and folding, however, is still poorly understood. Here we use a single-molecule optical tweezers approach to induce the selective unfolding of particular regions of T4 lysozyme and monitor the effect on other regions not directly acted on by force. We investigate how the topological organization of a protein (the order of structural elements along the sequence) affects the coupling and folding cooperativity between its domains. To probe the status of the regions not directly subjected to force, we determine the free energy changes during mechanical unfolding using Crooks’ fluctuation theorem. We pull on topological variants (circular permutants) and find that the topological organization of the polypeptide chain critically determines the folding cooperativity between domains and thus what parts of the folding/unfolding landscape are explored. We speculate that proteins may have evolved to select certain topologies that increase coupling between regions to avoid areas of the landscape that lead to kinetic trapping and misfolding.
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影响因子：
14.9
作者：
Lo WC;Lee CC;Lee CY;Lyu PC
通讯作者：
Lyu PC
DOI：
10.1073/pnas.0509217103
发表时间：
2006-01-31
影响因子：
11.1
作者：
Dietz, H;Rief, M
通讯作者：
Rief, M
DOI：
10.1073/pnas.97.1.139
发表时间：
2000-01-04
影响因子：
11.1
作者：
Yang, GL;Cecconi, C;Bustamante, C
通讯作者：
Bustamante, C
影响因子：
5.6
作者：
ZHANG, XJ;WOZNIAK, JA;MATTHEWS, BW
通讯作者：
MATTHEWS, BW
DOI：
10.1073/pnas.70.3.697
发表时间：
1973-01-01
影响因子：
11.1
作者：
WETLAUFE.DB
通讯作者：
WETLAUFE.DB