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PMID: 12620232 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule ends.

Molecular cell ·Vol. 11 ·No. 2 ·2003-02-00 ·Pages 445-57

Hunter AW, Caplow M, Coy DL, Hancock WO, Diez S, Wordeman L, Howard J

Abstract

MCAK belongs to the Kin I subfamily of kinesin-related proteins, a unique group of motor proteins that are not motile but instead destabilize microtubules. We show that MCAK is an ATPase that catalytically depolymerizes microtubules by accelerating, 100-fold, the rate of dissociation of tubulin from microtubule ends. MCAK has one high-affinity binding site per protofilament end, which, when occupied, has both the depolymerase and ATPase activities. MCAK targets protofilament ends very rapidly (on-rate 54 micro M(-1).s(-1)), perhaps by diffusion along the microtubule lattice, and, once there, removes approximately 20 tubulin dimers at a rate of 1 s(-1). We propose that up to 14 MCAK dimers assemble at the end of a microtubule to form an ATP-hydrolyzing complex that processively depolymerizes the microtubule.

MeSH Terms
Adenosine Triphosphate/metabolism Animals Binding Sites Hydrolysis In Vitro Techniques Kinesins/chemistry,metabolism Kinetics Microtubules/metabolism Models, Biological Osmolar Concentration Recombinant Proteins/chemistry,metabolism Tubulin/chemistry,metabolism
Chemicals
KIF2C protein, human Recombinant Proteins Tubulin Adenosine Triphosphate Kinesins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hunter Andrew W
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.
Caplow Michael
Coy David L
Hancock William O
Diez Stefan
Wordeman Linda
Howard Jonathon
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
Published
2003-02-00
Pages
445-57
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC6468321
Subset
IM
Grants
NIAMS NIH HHS · R37 AR040593 · United States
NIGMS NIH HHS · GM53654A · United States
NIAMS NIH HHS · AR40593 · United States
NIAMS NIH HHS · R01 AR040593 · United States
NIGMS NIH HHS · GM59231 · United States
NIGMS NIH HHS · R01 GM059231 · United States
PHS HHS · T326M07270 · United States
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