Force generation in kinesin hinges on cover-neck bundle formation
Force generation in kinesin hinges on cover-neck bundle formation
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DOI：
10.1016/j.str.2007.11.008
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发表时间：
2008-01-01
期刊：
影响因子：
5.7
通讯作者：
Karplus, Martin
中科院分区：
文献类型：
--
作者：
Hwang, Wonmuk;Lang, Matthew J.;Karplus, Martin
在驱动蛋白马达中，一个基本问题涉及ATP结合产生行走所需力的机制。可用的结构结合分子动力学模拟的分析表明，颈部接头的构象变化涉及九个残基长的N-末端区域，覆盖链，作为一个元素，是必不可少的力的产生。在ATP结合时，它与颈连接体形成β折叠，即盖-颈束，其诱导颈连接体的向前运动，随后与运动头形成闩锁型结合。从模型计算的估计失速力和各向异性响应的外部负载同意力钳测量。力产生的盖颈束形成的建议机制似乎适用于几个驱动蛋白家族。阐明了驱动蛋白作为已知最小的加工马达的设计原理。
In kinesin motors, a fundamental question concerns the mechanism by which ATP binding generates the force required for walking. Analysis of available structures combined with molecular dynamics simulations demonstrates that the conformational change of the neck linker involves the nine-residue-long N-terminal region, the cover strand, as an element that is essential for force generation. Upon ATP binding, it forms a beta sheet with the neck linker, the cover-neck bundle, which induces the forward motion of the neck linker, followed by a latch-type binding to the motor head. The estimated stall force and anisotropic response to external loads calculated from the model agree with force-clamp measurements. The proposed mechanism for force generation by the cover-neck bundle formation appears to apply to several kinesin families. It also elucidates the design principle of kinesin as the smallest known processive motor.