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Δευτέρα 10 Ιουλίου 2017

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

Publication date: 10 July 2017
Source:Developmental Cell, Volume 42, Issue 1
Author(s): Hugo Arellano-Santoyo, Elisabeth A. Geyer, Ema Stokasimov, Geng-Yuan Chen, Xiaolei Su, William Hancock, Luke M. Rice, David Pellman
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.

Teaser

Kinesin-8s promote length-dependent microtubule disassembly. Arellano and colleagues define a mechanism for Kip3/kinesin-8 depolymerization that involves a tubulin curvature-sensing binding switch. They propose that high affinity curved tubulin binding, which is accompanied by suppressed ATPse activity, enables its depolymerase activity. This Kip3 binding switch is thus central to Kip3's ability to selectively trim long microtubules, narrowing the length distribution of microtubules in cells.


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