Structural model for strain-dependent microtubule activation of Mg-ADP release from kinesin

Nat Struct Mol Biol. 2008 Oct;15(10):1067-75. doi: 10.1038/nsmb.1487. Epub 2008 Sep 21.


Mg-ADP release is considered to be a crucial process for the regulation and motility of kinesin. To gain insight into the structural basis of this process, we solved the atomic structures of kinesin superfamily protein-1A (KIF1A) during and after Mg(2+) release. On the basis of new structural and mutagenesis data, we propose a model mechanism for microtubule activation of Mg-ADP release from KIF1A. In our model, a specific interaction between loop L7 of KIF1A and beta-tubulin reconfigures the KIF1A active site by shifting the relative positions of switches I and II. This leads to the sequential release of a group of water molecules that sits over the Mg(2+) in the active site, followed by Mg(2+) and finally the ADP. We further propose that this set of events is linked to a strain-dependent docking of the neck linker to the motor core, which produces a two-step power stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / chemistry
  • Adenosine Diphosphate / metabolism*
  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Kinesins / chemistry
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Magnesium / chemistry
  • Magnesium / metabolism*
  • Mice
  • Microtubules / metabolism*
  • Models, Biological*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics
  • Phenotype
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • Kif1a protein, mouse
  • Adenosine Diphosphate
  • Kinesins
  • Magnesium

Associated data

  • PDB/2ZFI
  • PDB/2ZFJ
  • PDB/2ZFK
  • PDB/2ZFL
  • PDB/2ZFM