The C-terminal region of the motor protein MCAK controls its structure and activity through a conformational switch.
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.
Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Sandeep K
SK
Talapatra
Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Bethany
B
Harker
Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Julie P I
JP
Welburn
D000818:Animals; D016547:Kinesins / Q000737:chemistry* / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D011487:Protein Conformation; D061987:Sf9 Cells; D018411:Spodoptera
D016547:Kinesins
X-ray crystallography; biochemistry; biophysics; homo sapiens; human; kinesin; microtubule depolymerization; structural biology; structure; tubulin