A common mechanism for microtubule destabilizers - M type kinesins stabilize curling of the protofilament using the class-specific neck and loops
A common mechanism for microtubule destabilizers - M type kinesins stabilize curling of the protofilament using the class-specific neck and loops
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DOI：
10.1016/s0092-8674(04)00129-1
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发表时间：
2004-02-20
期刊：
影响因子：
64.5
通讯作者：
Hirokawa, N
中科院分区：
文献类型：
--
作者：
Ogawa, T;Nitta, R;Hirokawa, N
与其他驱动蛋白不同的是，中间运动域型驱动蛋白从微管的末端将微管分离。为了阐明其机制，我们解决了KIF 2C的X射线晶体结构，该家族的小鼠成员。确定了三个主要类别的具体特点。类特异性的N-末端颈部采用长而刚性的螺旋结构，垂直延伸到原丝间沟。这种结构解释了它在靶向微管末端和使原丝的横向相互作用不稳定方面的双重作用。L2环形成一个独特的指状结构，足够长和刚性，可以到达下一个微管蛋白亚基，以稳定原丝的剥离。开关I环的开放构象可以通过微管结合L 8环的移动而逆转，这表明其作为触发ATP水解的传感器的作用。突变分析支持这些结构的影响。
Unlike other kinesins, middle motor domain-type kinesins depolymerize the microtubule from its ends. To elucidate its mechanism, we solved the X-ray crystallographic structure of KIF2C, a murine member of this family. Three major class-specific features were identified. The class-specific N-terminal neck adopts a long and rigid helical structure extending out vertically into the interprotofilament groove. This structure explains its dual roles in targeting to the end of the microtubule and in destabilization of the lateral interaction of the protofilament. The loop L2 forms a unique finger-like structure, long and rigid enough to reach the next tubulin subunit to stabilize the peeling of the protofilament. The open conformation of the switch I loop could be reversed by the shift of the microtubule binding L8 loop, suggesting its role as the sensor to trigger ATP hydrolysis. Mutational analysis supports these structural implications.