title: The kinesin-13 MCAK has an unconventional ATPase cycle adapted for microtubule depolymerization.
abstract: Unlike other kinesins, members of the kinesin-13 subfamily do not move directionally along microtubules but, instead, depolymerize them. To understand how kinesins with structurally similar motor domains can have such dissimilar functions, we elucidated the ATP turnover cycle of the kinesin-13, MCAK. In contrast to translocating kinesins, ATP cleavage, rather than product release, is the rate-limiting step for ATP turnover by MCAK; unpolymerized tubulin and microtubules accelerate this step. Further, microtubule ends fully activate the ATPase by accelerating the exchange of ADP for ATP. This tuning of the cycle adapts MCAK for its depolymerization activity: lattice-stimulated ATP cleavage drives MCAK into a weakly bound nucleotide state that reaches microtubule ends by diffusion, and end-specific acceleration of nucleotide exchange drives MCAK into a strongly bound state that promotes depolymerization. This altered cycle accounts well for the different mechanical behaviour of this kinesin, which depolymerizes microtubules from their ends, compared to translocating kinesins that walk along microtubules. Thus, the kinesin motor domain is a nucleotide-dependent engine that can be differentially tuned for transport or depolymerization functions.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Claire T
authors.initials: CT
authors.lastname: Friel
authors.forename: Jonathon
authors.initials: J
authors.lastname: Howard
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007313:Insecta; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000737:chemistry
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C417670:KIF13A protein, human; D014404:Tubulin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D016547:Kinesins