Coiled-coil 1-mediated fastening of the neck and motor domains for kinesin-3 autoinhibition.
Coiled-coil 1-mediated fastening of the neck and motor domains for kinesin-3 autoinhibition.
复制标题
卷曲螺旋 1 介导的颈部和运动域紧固，用于驱动蛋白 3 自抑制。
DOI：
10.1073/pnas.1811209115
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Feng Wei
中科院分区：
文献类型：
--
作者：
Ren Jinqi;Wang Shuang;Chen Han;Wang Wenjuan;Huo Lin;Feng Wei
在Kinesin-3中，螺旋线圈1(CC1)可以隔离前一个颈部线圈(NC)进行自我抑制，但其潜在机制尚不清楚。在这里，我们确定了未被抑制的运动域(MD)-NC二聚体和被抑制的KIF13B的MD-NC-CC1单体的结构。在MD-NC-CC1单体中，CC1被裂解成两个短螺旋，意外地与NC和MD相互作用。与MD-NC二聚体相比，CC1介导的NC和MD的整合不仅阻止了NC二聚体的形成，而且还阻止了颈部连接物(NL)的脱接和ADP从MD释放。MD-NC-CC1单体中结构域间相互作用界面的基本残基的突变恢复了MD的活性。因此，CC1紧固颈域和MD，并抑制NC和NL。这种CC1介导的对整个颈域的锁定可能代表了一种适用于其他Kinesin-3发动机的Kinesin自抑制范例。
In kinesin-3, the coiled-coil 1 (CC1) can sequester the preceding neck coil (NC) for autoinhibition, but the underlying mechanism is poorly understood. Here, we determined the structures of the uninhibited motor domain (MD)-NC dimer and inhibited MD-NC-CC1 monomer of kinesin-3 KIF13B. In the MD-NC-CC1 monomer, CC1 is broken into two short helices that unexpectedly interact with both the NC and the MD. Compared with the MD-NC dimer, the CC1-mediated integration of NC and MD not only blocks the NC dimer formation, but also prevents the neck linker (NL) undocking and the ADP release from the MD. Mutations of the essential residues in the interdomain interaction interface in the MD-NC-CC1 monomer restored the MD activity. Thus, CC1 fastens the neck domain and MD and inhibits both NC and NL. This CC1-mediated lockdown of the entire neck domain may represent a paradigm for kinesin autoinhibition that could be applicable to other kinesin-3 motors.