The CC1-FHA Tandem as a Central Hub for Controlling the Dimerization and Activation of Kinesin-3 KIF1A

被引：46

作者：

Huo, Lin ^{[1
,2
]}

Yue, Yang ^{[1
,3
]}

Ren, Jinqi ^{[1
]}

Yu, Jiang ^{[2
]}

Liu, Junlin ^{[1
]}

Yu, Yong ^{[1
]}

Ye, Fei ^{[2
]}

Xu, Tao ^{[1
,3
]}

Zhang, Mingjie ^{[2
,4
]}

Feng, Wei ^{[1
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China

[2] Hong Kong Univ Sci & Technol, Div Life Sci, State Key Lab Mol Neurosci, Kowloon, Hong Kong, Peoples R China

[3] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China

[4] Hong Kong Univ Sci & Technol, Ctr Syst Biol & Human Hlth, Kowloon, Hong Kong, Peoples R China

来源：

STRUCTURE | 2012年 / 20卷 / 09期

基金：

中国国家自然科学基金;

关键词：

INTRACELLULAR-TRANSPORT; PROTEIN KIF1A; FHA DOMAIN; MOTOR; WALKING; MOVEMENT; SYSTEM; FAMILY; CELLS;

D O I：

10.1016/j.str.2012.07.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Kinesin-3 KIF1A plays prominent roles in axonal transport and synaptogenesis. KIF1A adopts a monomeric form in vitro but acts as a processive dimer in vivo. The mechanism underlying the motor dimerization is poorly understood. Here, we find that the CC1-FHA tandem of KIF1A exists as a stable dimer. The structure of CC1-FHA reveals that the linker between CC1 and FHA unexpectedly forms a beta-finger hairpin, which integrates CC1 with FHA assembling a CC1-FHA homodimer. More importantly, dissociation of the CC1-FHA dimer unleashes CC1 and the beta-finger, which are both essential for the motor inhibition. Thus, dimerization of the CC1-FHA tandem not only promotes the KIF1A dimer formation but also may trigger the motor activity via sequestering the CC1/beta-finger region. The CC1-FHA tandem likely functions as a hub for controlling the dimerization and activation of KIF1A, which may represent a new paradigm for the kinesin regulation shared by other kinesin-3 motors.

引用

页码：1550 / 1561

页数：12

共 32 条

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