The kinesin-13 MCAK has an unconventional ATPase cycle adapted for microtubule depolymerization

Friel, Claire T; Howard, Jonathon

Abstract

Unlike other kinesins, members of the kinesin-13 subfamily do not move directionally along microtubules but, instead, depolymerize them. To understand how kinesins with structurally similar motor domains can have such dissimilar functions, we elucidated the ATP turnover cycle of the kinesin-13, MCAK. In contrast to translocating kinesins, ATP cleavage, rather than product release, is the rate-limiting step for ATP turnover by MCAK; unpolymerized tubulin and microtubules accelerate this step. Further, microtubule ends fully activate the ATPase by accelerating the exchange of ADP for ATP. This tuning of the cycle adapts MCAK for its depolymerization activity: lattice-stimulated ATP cleavage drives MCAK into a weakly bound nucleotide state that reaches microtubule ends by diffusion, and end-specific acceleration of nucleotide exchange drives MCAK into a strongly bound state that promotes depolymerization. This altered cycle accounts well for the different mechanical behaviour of this kinesin, which depolymerizes microtubules from their ends, compared to translocating kinesins that walk along microtubules. Thus, the kinesin motor domain is a nucleotide-dependent engine that can be differentially tuned for transport or depolymerization functions. © 2011 European Molecular Biology Organization | All Rights Reserved.

Citation

Friel, C. T., & Howard, J. (2011). The kinesin-13 MCAK has an unconventional ATPase cycle adapted for microtubule depolymerization. EMBO Journal, 30(19), 3928-3939. https://doi.org/10.1038/emboj.2011.290

• Journal Article Type: Article
• Acceptance Date: Jul 18, 2011
• Online Publication Date: Aug 26, 2011
• Publication Date: Oct 5, 2011
• Deposit Date: Aug 11, 2022
• Publicly Available Date: Aug 11, 2022
• Journal: EMBO Journal
• Print ISSN: 0261-4189
• Electronic ISSN: 1460-2075
• Publisher: EMBO Press
• Peer Reviewed: Peer Reviewed
• Volume: 30
• Issue: 19
• Pages: 3928-3939
• DOI: https://doi.org/10.1038/emboj.2011.290
• Public URL: https://nottingham-repository.worktribe.com/output/3182572
• Publisher URL: https://www.embopress.org/doi/full/10.1038/emboj.2011.290