Pathways and kinetic barriers in mechanical unfolding and refolding of RNA and proteins
Pathways and kinetic barriers in mechanical unfolding and refolding of RNA and proteins
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DOI：
10.1016/j.str.2006.09.002
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发表时间：
2006-11-01
期刊：
影响因子：
5.7
通讯作者：
Thirumalai, D.
中科院分区：
文献类型：
--
作者：
Hyeon, Changbong;Dima, Ruxandra I.;Thirumalai, D.
利用自组织聚合物模型，我们预测了核酶和绿色荧光蛋白的机械展开和复性途径。与实验一致的是，四膜虫核酶有6到8个展开的转变。根据加载速度的不同，固氮弧菌核酶在力梯展开过程中的裂解次数在2到4之间。四膜虫核酶P4-P6亚区的强制猝灭复性是通过一个紧密的中间体发生的。随后在螺旋P5b-P6a和P5a/P5c-P4之间形成三级接触导致本征状态。力猝灭折叠路径与系综实验一致。在主导的去折叠途径中，GFP的N端α螺旋首先解开，然后是N端的β链断裂。还有第三种中间体，它涉及另外三条链的破坏。与实验一致的是，GFP的力淬重折叠路径是分层的，限速步骤是桶的关闭。
Using self-organized polymer models, we predict mechanical unfolding and refolding pathways of ribozymes, and the green fluorescent protein. In agreement with experiments, there are between six and eight unfolding transitions in the Tetrahymena ribozyme. Depending on the loading rate, the number of rips in the force-ramp unfolding of the Azoarcus ribozymes is between two and four. Force-quench refolding of the P4-P6 subdomain of the Tetrahymena ribozyme occurs through a compact intermediate. Subsequent formation of tertiary contacts between helices P5b-P6a and P5a/P5c-P4 leads to the native state. The force-quench refolding pathways agree with ensemble experiments. In the dominant unfolding route, the N-terminal alpha helix of GFP unravels first, followed by disruption of the N terminus beta strand. There is a third intermediate that involves disruption of three other strands. In accord with experiments, the force-quench refolding pathway of GFP is hierarchic, with the rate-limiting step being the closure of the barrel.