title: Regulation of KinI kinesin ATPase activity by binding to the microtubule lattice.
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.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Moores
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hekmat-Nejad
authors.forename: Roman
authors.initials: R
authors.lastname: Sakowicz
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Milligan
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D020285:Cryoelectron Microscopy; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D046911:Macromolecular Substances; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D046911:Macromolecular Substances; D020409:Molecular Motor Proteins; D015800:Protozoan Proteins; D014404:Tubulin; D000251:Adenosine Triphosphatases; D016547:Kinesins