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

23 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

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A Tubulin Binding Switch Underlies Kip3/Kinesin-8 Depolymerase Activity'. Together they form a unique fingerprint.

  • Cite this

    Arellano-Santoyo, H., Geyer, E. A., Stokasimov, E., Chen, G. Y., Su, X., Hancock, W., Rice, L. M., & Pellman, D. (2017). A Tubulin Binding Switch Underlies Kip3/Kinesin-8 Depolymerase Activity. Developmental Cell, 42(1), 37-51.e8. https://doi.org/10.1016/j.devcel.2017.06.011