The structure of the kinesin-1 motor-tail complex reveals the mechanism of autoinhibition

Science. 2011 Aug 12;333(6044):883-5. doi: 10.1126/science.1204824.

Abstract

When not transporting cargo, kinesin-1 is autoinhibited by binding of a tail region to the motor domains, but the mechanism of inhibition is unclear. We report the crystal structure of a motor domain dimer in complex with its tail domain at 2.2 angstroms and compare it with a structure of the motor domain alone at 2.7 angstroms. These structures indicate that neither an induced conformational change nor steric blocking is the cause of inhibition. Instead, the tail cross-links the motor domains at a second position, in addition to the coiled coil. This "double lockdown," by cross-linking at two positions, prevents the movement of the motor domains that is needed to undock the neck linker and release adenosine diphosphate. This autoinhibition mechanism could extend to some other kinesins.

Publication types

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

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Amino Acid Sequence
  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Drosophila Proteins / antagonists & inhibitors*
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / metabolism
  • Hydrogen Bonding
  • Kinesins / antagonists & inhibitors*
  • Kinesins / chemistry*
  • Kinesins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization
  • Protein Structure, Tertiary

Substances

  • Drosophila Proteins
  • Adenosine Diphosphate
  • Khc protein, Drosophila
  • Kinesins

Associated data

  • PDB/2Y5W
  • PDB/2Y65