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

15 Citations (Scopus)

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

Fingerprint

Kinesin
Tubulin
Microtubules
Switches
Depolymerization
Saccharomycetales
Yeast
Adenosine Triphosphatases
Cellular Structures
Conformations
Hydrolysis
Identification (control systems)
Adenosine Triphosphate

Keywords

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

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Arellano-Santoyo, H., Geyer, E. A., Stokasimov, E., Chen, G. Y., Su, X., Hancock, W., ... 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

A Tubulin Binding Switch Underlies Kip3/Kinesin-8 Depolymerase Activity. / Arellano-Santoyo, Hugo; Geyer, Elisabeth A.; Stokasimov, Ema; Chen, Geng Yuan; Su, Xiaolei; Hancock, William; Rice, Luke M.; Pellman, David.

In: Developmental Cell, Vol. 42, No. 1, 10.07.2017, p. 37-51.e8.

Research output: Contribution to journalArticle

Arellano-Santoyo, H, Geyer, EA, Stokasimov, E, Chen, GY, Su, X, Hancock, W, Rice, LM & Pellman, D 2017, 'A Tubulin Binding Switch Underlies Kip3/Kinesin-8 Depolymerase Activity', Developmental Cell, vol. 42, no. 1, pp. 37-51.e8. https://doi.org/10.1016/j.devcel.2017.06.011
Arellano-Santoyo H, Geyer EA, Stokasimov E, Chen GY, Su X, Hancock W et al. A Tubulin Binding Switch Underlies Kip3/Kinesin-8 Depolymerase Activity. Developmental Cell. 2017 Jul 10;42(1):37-51.e8. https://doi.org/10.1016/j.devcel.2017.06.011
Arellano-Santoyo, Hugo ; Geyer, Elisabeth A. ; Stokasimov, Ema ; Chen, Geng Yuan ; Su, Xiaolei ; Hancock, William ; Rice, Luke M. ; Pellman, David. / A Tubulin Binding Switch Underlies Kip3/Kinesin-8 Depolymerase Activity. In: Developmental Cell. 2017 ; Vol. 42, No. 1. pp. 37-51.e8.
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