Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms

J Cell Biol. 2010 Jun 14;189(6):1013-25. doi: 10.1083/jcb.201001057. Epub 2010 Jun 7.

Abstract

Long-distance transport in cells is driven by kinesin and dynein motors that move along microtubule tracks. These motors must be tightly regulated to ensure the spatial and temporal fidelity of their transport events. Transport motors of the kinesin-1 and kinesin-3 families are regulated by autoinhibition, but little is known about the mechanisms that regulate kinesin-2 motors. We show that the homodimeric kinesin-2 motor KIF17 is kept in an inactive state in the absence of cargo. Autoinhibition is caused by a folded conformation that enables nonmotor regions to directly contact and inhibit the enzymatic activity of the motor domain. We define two molecular mechanisms that contribute to autoinhibition of KIF17. First, the C-terminal tail interferes with microtubule binding; and second, a coiled-coil segment blocks processive motility. The latter is a new mechanism for regulation of kinesin motors. This work supports the model that autoinhibition is a general mechanism for regulation of kinesin motors involved in intracellular trafficking events.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Humans
  • Kinesins / antagonists & inhibitors*
  • Kinesins / chemistry*
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Microtubules / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation*
  • Protein Multimerization
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • KIF17 protein, human
  • Recombinant Fusion Proteins
  • Kinesins