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The depolymerase activity of MCAK shows graded response to Aurora B kinase phosphorylation through allosteric regulation

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Original languageEnglish
Number of pages8
JournalJournal of Cell Science
Volume132
Issue number4
Early online date21 Dec 2018
DOIs
Publication statusPublished - 14 Jan 2019

Abstract

Kinesin-13 motors regulate precise microtubule dynamics and limit microtubule
length throughout metazoans by depolymerizing microtubule ends. Recently,
MCAK has been proposed to undergo large conformational changes during its
catalytic cycle, as it switches from solution to bound state. Here, we reveal that
MCAK has a compact conformation in solution using crosslinking and electron
microscopy. When MCAK is bound to the microtubule ends, it adopts an
extended conformation with the N terminus and neck region of MCAK interacting
with the microtubule. Interestingly, the region of MCAK that interacts with the
microtubule is the region phosphorylated by Aurora B and contains an EBbinding
motif. The level of phosphorylation of the N terminus results in a graded
microtubule depolymerase activity. Here we show the N terminus of MCAK forms
a platform to integrate Aurora B kinase downstream signals and in response finetunes its depolymerase activity during mitosis. We propose that this allosteric control mechanism allows decoupling of the N terminus from the motor domain of MCAK to allow MCAK depolymerase activity at kinetochores.

    Research areas

  • MCAK, Aurora B, microtubules, phosphorylation

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