Edinburgh Research Explorer

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

Research output: Contribution to journalArticle

Related Edinburgh Organisations

Open Access permissions



  • Download as Adobe PDF

    Proof, 2.21 MB, PDF document

  • Download as Adobe PDF

    Rights statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

    Final published version, 4.69 MB, PDF document

    Licence: Creative Commons: Attribution (CC-BY)

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


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

Download statistics

No data available

ID: 77907657