Developmental Cell
Volume 42, Issue 1, 10 July 2017, Pages 37-51.e8
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Article
A Tubulin Binding Switch Underlies Kip3/Kinesin-8 Depolymerase Activity

https://doi.org/10.1016/j.devcel.2017.06.011Get rights and content
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Highlights

  • A tubulin binding switch enables length-dependent microtubule disassembly by Kip3

  • Tubulin binding suppresses Kip3 ATPase activity, promoting depolymerase activity

  • Loop11 sequence in Kip3 is necessary and sufficient for curved tubulin binding

  • Kip3 disassembly-resistant microtubules support the two-state binding switch model

Summary

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

microtubule dynamics
kinesins
microtubule associated proteins
depolymerization
spindle scaling

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These authors contributed equally

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