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PMID: 14662742 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Regulation of KinI kinesin ATPase activity by binding to the microtubule lattice.

The Journal of cell biology ·Vol. 163 ·No. 5 ·2003-12-08 ·Pages 963-71

Moores CA, Hekmat-Nejad M, Sakowicz R, Milligan RA

Abstract

KinI kinesins are important in regulating the complex dynamics of the microtubule cytoskeleton. They are unusual in that they depolymerize, rather than move along microtubules. To determine the attributes of KinIs that distinguish them from translocating kinesins, we examined the ATPase activity, microtubule affinity, and three-dimensional microtubule-bound structure of a minimal KinI motor domain. Together, the kinetic, affinity, and structural data lead to the conclusion that on binding to the microtubule lattice, KinIs release ADP and enter a stable, low-affinity, regulated state, from which they do not readily progress through the ATPase cycle. This state may favor detachment, or diffusion of the KinI to its site of action, the microtubule ends. Unlike conventional translocating kinesins, which are microtubule lattice-stimulated ATPases, it seems that with KinIs, nucleotide-mediated modulation of tubulin affinity is only possible when it is coupled to protofilament deformation. This provides an elegant mechanistic basis for their unique depolymerizing activity.

MeSH Terms
Adenosine Triphosphatases/metabolism Animals Cryoelectron Microscopy Kinesins/chemistry,metabolism Macromolecular Substances Microtubules/chemistry,metabolism Models, Molecular Molecular Motor Proteins/metabolism Plasmodium falciparum/metabolism Protein Binding Protein Conformation Protozoan Proteins/metabolism Tubulin/metabolism
Chemicals
Macromolecular Substances Molecular Motor Proteins Protozoan Proteins Tubulin Adenosine Triphosphatases Kinesins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Moores Carolyn A
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hekmat-Nejad Mohammad
Sakowicz Roman
Milligan Ronald A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
2003-12-08
Pages
963-71
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173608
Subset
IM
Grants
NIGMS NIH HHS · GM-52468 · United States
NIGMS NIH HHS · R01 GM061939 · United States
NCRR NIH HHS · P41 RR017573 · United States
NIGMS NIH HHS · GM61939 · United States
NCRR NIH HHS · RR17573 · United States
NIGMS NIH HHS · R01 GM052468 · United States
NIGMS NIH HHS · R37 GM052468 · United States
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