Hwang Wonmuk, Lang Matthew J, Karplus Martin
Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA.
Structure. 2008 Jan;16(1):62-71. doi: 10.1016/j.str.2007.11.008.
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.
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。对现有结构的分析结合分子动力学模拟表明，颈部连接体的构象变化涉及九个残基长的N端区域，即覆盖链，它是产生力的关键元素。ATP结合后，它与颈部连接体形成一个β折叠，即覆盖-颈部束，这会诱导颈部连接体向前运动，随后以闩锁型方式与马达头部结合。根据该模型计算出的估计失速力和对外部负载的各向异性响应与力钳测量结果相符。所提出的由覆盖-颈部束形成产生力的机制似乎适用于多个驱动蛋白家族。它还阐明了驱动蛋白作为已知最小的持续性马达的设计原理。
