Structural model for strain-dependent microtubule activation of Mg-ADP release from kinesin
Structural model for strain-dependent microtubule activation of Mg-ADP release from kinesin
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DOI：
10.1038/nsmb.1487
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发表时间：
2008-10-01
影响因子：
16.8
通讯作者：
Hirokawa, Nobutaka
中科院分区：
文献类型：
--
作者：
Nitta, Ryo;Okada, Yasushi;Hirokawa, Nobutaka
Mg-ADP的释放被认为是驱动蛋白的调节和运动的关键过程。为了深入了解这一过程的结构基础，我们解决了驱动蛋白超家族蛋白-1A（KIF 1A）在Mg 2+释放期间和之后的原子结构。新的结构和诱变数据的基础上，我们提出了一个模型机制的微管激活的Mg-ADP从KIF 1A释放。在我们的模型中，KIF 1A的L7环和β-微管蛋白之间的特定相互作用通过改变开关I和II的相对位置来重新配置KIF 1A活性位点。这导致了一组水分子的顺序释放，这些水分子位于活性位点中的Mg 2+上，然后是Mg 2+，最后是ADP。我们进一步提出，这一组事件是链接到一个应变依赖性对接的颈部连接器的电机核心，这产生了两步动力冲程。
Mg-ADP release is considered to be a crucial process for the regulation and motility of kinesin. To gain insight into the structural basis of this process, we solved the atomic structures of kinesin superfamily protein-1A (KIF1A) during and after Mg2+ release. On the basis of new structural and mutagenesis data, we propose a model mechanism for microtubule activation of Mg-ADP release from KIF1A. In our model, a specific interaction between loop L7 of KIF1A and beta-tubulin reconfigures the KIF1A active site by shifting the relative positions of switches I and II. This leads to the sequential release of a group of water molecules that sits over the Mg2+ in the active site, followed by Mg2+ and finally the ADP. We further propose that this set of events is linked to a strain-dependent docking of the neck linker to the motor core, which produces a two-step power stroke.