Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin
Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin
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apo 状态下 Zen4 的晶体结构揭示了驱动蛋白缺失的构象
DOI：
10.1038/ncomms14951
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发表时间：
2017-04-10
影响因子：
16.6
通讯作者：
Chen, Zhucheng
中科院分区：
文献类型：
--
作者：
Guan, Ruifang;Zhang, Lei;Chen, Zhucheng
驱动蛋白水解ATP以沿沿着微管运输细胞内货物。驱动蛋白颈连接体（NL）通过ATP酶循环改变其构象而作为中心机械化学偶联元件发挥功能。在这里，我们报告了驱动蛋白-6 Zen 4在无核苷酸，载脂蛋白状态下的晶体结构，NL初始片段（NIS）采用向后对接的构象，前面的α6螺旋部分熔化。单分子荧光共振能量转移（smFRET）分析表明，NIS的驱动蛋白-1经历了类似的构象变化，在张力下的双头结合（2 HB）状态，而它在很大程度上是无序的没有张力。NIS的后向对接结构对于运动的运动性是必不可少的。我们的研究结果揭示了驱动蛋白的关键缺失构象，这提供了稳定的2 HB状态的结构基础，并为最佳NL长度提供了基于张力的理论基础，以确保马达的持续合成能力。
Kinesins hydrolyse ATP to transport intracellular cargoes along microtubules. Kinesin neck linker (NL) functions as the central mechano-chemical coupling element by changing its conformation through the ATPase cycle. Here we report the crystal structure of kinesin-6 Zen4 in a nucleotide-free, apo state, with the NL initial segment (NIS) adopting a backward-docked conformation and the preceding α6 helix partially melted. Single-molecule fluorescence resonance energy transfer (smFRET) analyses indicate the NIS of kinesin-1 undergoes similar conformational changes under tension in the two-head bound (2HB) state, whereas it is largely disordered without tension. The backward-docked structure of NIS is essential for motility of the motor. Our findings reveal a key missing conformation of kinesins, which provides the structural basis of the stable 2HB state and offers a tension-based rationale for an optimal NL length to ensure processivity of the motor.