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The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule
Andrew W Hunter1, Michael Caplow, David L Coy
1Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.
Abstract:
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.
Insights
Microtubule-depolymerizing kinesin-like protein 1 (MCAK) is an ATPase that accelerates tubulin dissociation from microtubule ends. It forms a complex to depolymerize microtubules, acting as a crucial microtubule destabilizer.
Area of Science:
- Cell Biology
- Molecular Motors
- Cytoskeleton Dynamics
Background:
- Microtubule dynamics are critical for cellular processes.
- Kinesin motor proteins play diverse roles in cell biology.
- MCAK is a member of the Kin I kinesin subfamily, known for microtubule destabilization.
Purpose of the Study:
- To elucidate the mechanism by which MCAK depolymerizes microtubules.
- To characterize the ATPase activity of MCAK in relation to microtubule dynamics.
- To understand the binding and catalytic properties of MCAK at microtubule ends.
Main Methods:
- Biochemical assays to measure ATPase activity.
- Microtubule depolymerization rate measurements.
- Kinetic analysis of MCAK binding to microtubules.
Main Results:
- MCAK functions as an ATPase that accelerates tubulin dissociation from microtubule ends by 100-fold.
- MCAK binds with high affinity to protofilament ends, exhibiting both depolymerase and ATPase activities.
- MCAK rapidly targets microtubule ends and removes tubulin dimers processively.
Conclusions:
- MCAK acts as a potent microtubule depolymerase through its ATPase activity.
- MCAK likely assembles into a complex at microtubule ends to facilitate processive depolymerization.
- These findings reveal MCAK's role in regulating microtubule stability.