4.7 Article

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

期刊

STRUCTURE
卷 20, 期 9, 页码 1550-1561

出版社

CELL PRESS
DOI: 10.1016/j.str.2012.07.002

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资金

  1. National Major Basic Research Program of China [2011CB910503]
  2. National Natural Science Foundation of China [31070657, 31190062]
  3. Knowledge Innovation Program of the Chinese Academy of Sciences [KSCX2-YW-R-154, KSCX2-EW-J-3]
  4. Research Grants Council of Hong Kong [664009, 660709, 663610, HKUST6/CRF/10, SEG_HKUST06, AoE/B-15/01-II]

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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.

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