The C-terminal region of the motor protein MCAK controls its structure and activity through a conformational switch

  1. Sandeep K Talapatra
  2. Bethany Harker
  3. Julie P I Welburn  Is a corresponding author
  1. University of Edinburgh, United Kingdom

Abstract

The precise regulation of microtubule dynamics is essential during cell division. The kinesin-13 motor protein MCAK is a potent microtubule depolymerase. The divergent non-motor regions flanking the ATPase domain are critical in regulating its targeting and activity. However, the molecular basis for the function of the non-motor regions within the context of full-length MCAK is unknown. Here we determine the structure of MCAK motor domain bound to its regulatory C-terminus. Our analysis reveals that the MCAK C-terminus binds to two motor domains in solution and is displaced allosterically upon microtubule binding, which allows its robust accumulation at microtubule ends. These results demonstrate that MCAK undergoes long-range conformational changes involving its C-terminus during the soluble to microtubule-bound transition and that the C-terminus-motor interaction represents a structural intermediate in the MCAK catalytic cycle. Together, our work reveals intrinsic molecular mechanisms underlying the regulation of kinesin-13 activity.

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Author details

  1. Sandeep K Talapatra

    Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Bethany Harker

    Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Julie P I Welburn

    Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    julie.welburn@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2015, Talapatra et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Sandeep K Talapatra
  2. Bethany Harker
  3. Julie P I Welburn
(2015)
The C-terminal region of the motor protein MCAK controls its structure and activity through a conformational switch
eLife 4:e06421.
https://doi.org/10.7554/eLife.06421

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https://doi.org/10.7554/eLife.06421