The CC1-FHA tandem as a central hub for controlling the dimerization and activation of kinesin-3 KIF1A

Structure. 2012 Sep 5;20(9):1550-61. doi: 10.1016/j.str.2012.07.002. Epub 2012 Aug 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Conserved Sequence
  • Crystallography, X-Ray
  • Enzyme Activation
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Kinesin / chemistry*
  • Kinesin / genetics
  • Kinesin / metabolism
  • Mice
  • Microtubules / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization*
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Protein Transport

Substances

  • KIF1A protein, human
  • Kinesin

Associated data

  • PDB/4EGX
  • PDB/4EJQ