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

1 janv. 2018Journal of Cell Science

DOI : 10.1242/jcs.228353

Auteurs

Toni McHugh, Juan Zou, Vladimir A. Volkov, Aurélie Bertin, Juri Rappsilber, Marileen Dogterom, Julie P. I. Welburn

Résumé

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 EB-binding 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 fine-tunes 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.

Membres

AURELIE BERTIN

Directeur de recherche CNRS