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

Hugo Arellano-Santoyo, Elisabeth A. Geyer, Ema Stokasimov, Geng Yuan Chen, Xiaolei Su, William Hancock, Luke M. Rice, David Pellman

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)37-51.e8
JournalDevelopmental Cell
Volume42
Issue number1
DOIs
StatePublished - Jul 10 2017

Keywords

  • depolymerization
  • kinesins
  • microtubule associated proteins
  • microtubule dynamics
  • spindle scaling

ASJC Scopus subject areas

  • Developmental Biology

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