title: The CC1-FHA tandem as a central hub for controlling the dimerization and activation of kinesin-3 KIF1A.
abstract: 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 β-finger hairpin, which integrates CC1 with FHA assembling a CC1-FHA homodimer. More importantly, dissociation of the CC1-FHA dimer unleashes CC1 and the β-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/β-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.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Huo
authors.forename: Yang
authors.initials: Y
authors.lastname: Yue
authors.forename: Jinqi
authors.initials: J
authors.lastname: Ren
authors.forename: Jiang
authors.initials: J
authors.lastname: Yu
authors.forename: Junlin
authors.initials: J
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021381:Protein Transport
chemical_list: C094065:KIF1A protein, human; D016547:Kinesins