The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule ends.
MCAK belongs to the Kin I subfamily of kinesin-related proteins, a unique group of motor proteins that are not motile but instead destabilize microtubules. We show that MCAK is an ATPase that catalytically depolymerizes microtubules by accelerating, 100-fold, the rate of dissociation of tubulin from microtubule ends. MCAK has one high-affinity binding site per protofilament end, which, when occupied, has both the depolymerase and ATPase activities. MCAK targets protofilament ends very rapidly (on-rate 54 micro M(-1).s(-1)), perhaps by diffusion along the microtubule lattice, and, once there, removes approximately 20 tubulin dimers at a rate of 1 s(-1). We propose that up to 14 MCAK dimers assemble at the end of a microtubule to form an ATP-hydrolyzing complex that processively depolymerizes the microtubule.
Hunter
Andrew W
AW
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.
Caplow
Michael
M
Coy
David L
DL
Hancock
William O
WO
Diez
Stefan
S
Wordeman
Linda
L
Howard
Jonathon
J
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D006868:Hydrolysis; D066298:In Vitro Techniques; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D009994:Osmolar Concentration; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
C091489:KIF2C protein, human; D011994:Recombinant Proteins; D014404:Tubulin; D000255:Adenosine Triphosphate; D016547:Kinesins