C-terminus of mitotic centromere-associated kinesin (MCAK) inhibits its lattice-stimulated ATPase activity

The Biochemical Journal
Ayana Moore, Linda Wordeman

Abstract

Mitotic centromere-associated kinesin (MCAK) is a microtubule (MT)-destabilizing molecular motor. In the present study we show that the final 8 amino acids of the C-terminus of MCAK inhibit lattice-stimulated ATPase activity of the motor. Surprisingly, loss of this C-terminal 'tail' (MCAK-Q710) leads to more rapid depolymerization of MTs relative to full-length MCAK (wt-MCAK). Biochemical and microscopic assays revealed that MCAK-Q710 bound to the MT lattice with higher apparent affinity as compared with wt-MCAK. End-stimulated depolymerization was similar for both enzymes. These data suggest that lattice-bound MCAK can increase the rate of MT depolymerization, but at an energy cost. The function of the C-terminus of MCAK may be to selectively inhibit lattice-stimulated ATPase activity, resulting in limited interactions of the motor with the MT lattice. This increases the coupling between ATP hydrolysis and tubulin dimer release, but it also limits MT depolymerization.

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Citations

Mar 7, 2008·Nature Reviews. Molecular Cell Biology·Anna Akhmanova, Michel O Steinmetz
Dec 8, 2009·Nature Structural & Molecular Biology·Jeremy R CooperLinda Wordeman
Nov 18, 2005·Molecular Biology of the Cell·Kathleen M HertzerClaire E Walczak
Nov 10, 2006·Molecular Biology of the Cell·Stephanie C Ems-McClungClaire E Walczak
Jul 24, 2013·Annual Review of Cell and Developmental Biology·Claire E WalczakRyoma Ohi
May 11, 2005·The Journal of Cell Biology·Ayana T MooreLinda Wordeman
Nov 13, 2008·The Journal of Cell Biology·Michael WagenbachJeremy Cooper
Jul 1, 2009·The Journal of Cell Biology·Leticia PerisAnnie Andrieux
Apr 1, 2009·The Journal of Cell Biology·Anke M MulderRonald A Milligan
Oct 18, 2011·Seminars in Cell & Developmental Biology·Douglas R Drummond
Aug 26, 2011·Bioarchitecture·Marvin E TanenbaumAnna Akhmanova
Dec 3, 2013·Current Biology : CB·Stephanie C Ems-McClungClaire E Walczak
Mar 5, 2016·Molecular Biology of the Cell·Hailing ZongStephanie C Ems-McClung
Nov 29, 2016·ELife·Keisuke IshiharaTimothy J Mitchison
Mar 17, 2017·Molecular Biology of the Cell·Lauren D'AngeloKenneth A Myers
Aug 16, 2017·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Valeri BarsegovRuxandra I Dima
Nov 24, 2018·Biochemical Society Transactions·Claire T Friel, Julie P Welburn
Jul 16, 2008·Physiological Reviews·Nobutaka Hirokawa, Yasuko Noda
Sep 22, 2006·Journal of Cell Science·Carolyn A Moores, Ronald A Milligan
Sep 29, 2004·Trends in Cell Biology·Ayana Moore, Linda Wordeman

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