A Tubulin Binding Switch Underlies Kip3/Kinesin-8 Depolymerase Activity

Dev Cell. 2017 Jul 10;42(1):37-51.e8. doi: 10.1016/j.devcel.2017.06.011.


Kinesin-8 motors regulate the size of microtubule structures, using length-dependent accumulation at the plus end to preferentially disassemble long microtubules. Despite extensive study, the kinesin-8 depolymerase mechanism remains under debate. Here, we provide evidence for an alternative, tubulin curvature-sensing model of microtubule depolymerization by the budding yeast kinesin-8, Kip3. Kinesin-8/Kip3 uses ATP hydrolysis, like other kinesins, for stepping on the microtubule lattice, but at the plus end Kip3 undergoes a switch: its ATPase activity is suppressed when it binds tightly to the curved conformation of tubulin. This prolongs plus-end binding, stabilizes protofilament curvature, and ultimately promotes microtubule disassembly. The tubulin curvature-sensing model is supported by our identification of Kip3 structural elements necessary and sufficient for plus-end binding and depolymerase activity, as well as by the identification of an α-tubulin residue specifically required for the Kip3-curved tubulin interaction. Together, these findings elucidate a major regulatory mechanism controlling the size of cellular microtubule structures.

Keywords: depolymerization; kinesins; microtubule associated proteins; microtubule dynamics; spindle scaling.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Biocatalysis
  • Hydrolysis
  • Kinesins / chemistry
  • Kinesins / metabolism*
  • Microtubules / metabolism
  • Models, Biological
  • Models, Molecular
  • Mutant Proteins / metabolism
  • Polymerization
  • Protein Binding
  • Protein Structure, Secondary
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sus scrofa
  • Tubulin / metabolism*


  • KIP3 protein, S cerevisiae
  • Mutant Proteins
  • Saccharomyces cerevisiae Proteins
  • Tubulin
  • Adenosine Triphosphate
  • Kinesins