Hannah R. Belsham
A Cdk1 phosphomimic mutant of MCAK impairs microtubule end recognition
Belsham, Hannah R.; Friel, Claire T.
Abstract
The microtubule depolymerising kinesin-13, MCAK, is phosphorylated at residue T537 by Cdk1. This is the only known phosphorylation site within MCAK’s motor domain. To understand the impact of phosphorylation by Cdk1 microtubule depolymerisation activity, we have investigated the molecular mechanism of the phosphomimic mutant T537E. This mutant significantly impairs microtubule depolymerisation activity and when transfected into cells causes metaphase arrest and misaligned chromosomes. We show that the molecular mechanism underlying the reduced depolymerisation activity of this phosphomimic mutant is an inability to recognise the microtubule end. The microtubule-end residence time is reduced relative to wild-type MCAK, whereas the lattice residence time is unchanged by the phosphomimic mutation. Further, the microtubule-end specific stimulation of ADP dissociation, characteristic of MCAK, is abolished by this mutation. Our data shows that T537E is unable to distinguish between the microtubule end and the microtubule lattice.
Other Type | Other |
---|---|
Acceptance Date | Nov 28, 2017 |
Online Publication Date | Dec 6, 2017 |
Publication Date | Dec 6, 2017 |
Deposit Date | May 8, 2019 |
Publisher | Cold Spring Harbor Laboratory Press |
DOI | https://doi.org/10.1101/188425 |
Public URL | https://nottingham-repository.worktribe.com/output/1874150 |
Additional Information | preprint in bioRxiv |
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