title: C-terminus of mitotic centromere-associated kinesin (MCAK) inhibits its lattice-stimulated ATPase activity.
abstract: Mitotic centromere-associated kinesin (MCAK) is a microtubule (MT)-destabilizing molecular motor. In the present study we show that the final 8 amino acids of the C-terminus of MCAK inhibit lattice-stimulated ATPase activity of the motor. Surprisingly, loss of this C-terminal 'tail' (MCAK-Q710) leads to more rapid depolymerization of MTs relative to full-length MCAK (wt-MCAK). Biochemical and microscopic assays revealed that MCAK-Q710 bound to the MT lattice with higher apparent affinity as compared with wt-MCAK. End-stimulated depolymerization was similar for both enzymes. These data suggest that lattice-bound MCAK can increase the rate of MT depolymerization, but at an energy cost. The function of the C-terminus of MCAK may be to selectively inhibit lattice-stimulated ATPase activity, resulting in limited interactions of the motor with the MT lattice. This increases the coupling between ATP hydrolysis and tubulin dimer release, but it also limits MT depolymerization.
authors.affiliation: Department of Physiology and Biophysics, University of Washington School of Medicine, 1959 NE Pacific St., Box 357290, Seattle, WA 98195, USA. atmoore@u.washington.edu
authors.forename: Ayana
authors.initials: A
authors.lastname: Moore
authors.forename: Linda
authors.initials: L
authors.lastname: Wordeman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002478:Cells, Cultured; D002503:Centromere / Q000378:metabolism; D006224:Cricetinae; D019281:Dimerization; D006868:Hydrolysis; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D012235:Rhodamines / Q000378:metabolism; D017384:Sequence Deletion; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D012235:Rhodamines; D014404:Tubulin; C490417:mitotic centromere-associated kinesin, hamster; D000255:Adenosine Triphosphate; D016547:Kinesins