title: Catalysis of the microtubule on-rate is the major parameter regulating the depolymerase activity of MCAK.
abstract: The kinesin-13, MCAK, is a critical regulator of microtubule dynamics in eukaryotic cells. We have functionally dissected the structural features responsible for MCAK's potent microtubule depolymerization activity. MCAK's positively charged neck enhances its delivery to microtubule ends not by tethering the molecule to microtubules during diffusion, as commonly thought, but by catalyzing the association of MCAK to microtubules. On the other hand, this same positively charged neck slightly diminishes MCAK's ability to remove tubulin subunits once at the microtubule end. Conversely, dimerization reduces MCAK delivery but improves MCAK's ability to remove tubulin subunits. The reported kinetics for these events predicts a nonspecific binding mechanism that may represent a paradigm for the diffusive interaction of many microtubule-binding proteins.
authors: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington, USA.
authors: Jeremy R
authors: JR
authors: Cooper
authors: Michael
authors: M
authors: Wagenbach
authors: Charles L
authors: CL
authors: Asbury
authors: Linda
authors: L
authors: Wordeman
mesh_terms: D000818:Animals; D002384:Catalysis; D006224:Cricetinae; D003412:Cricetulus; D019281:Dimerization; D007091:Image Processing, Computer-Assisted; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D038761:Photobleaching; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014404:Tubulin; C490417:mitotic centromere-associated kinesin, hamster; D016547:Kinesins