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

Sandeep K. Talapatra, Bethany Harker, Julie P I Welburn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere06421
Number of pages55
JournaleLIFE
Volume4
DOIs
Publication statusPublished - 27 Apr 2015

Keywords

  • kinesin-13
  • microtubule
  • microtubule depolymerase
  • mitosis
  • self-interaction
  • X-ray structure

Fingerprint

Dive into the research topics of 'The C-terminal region of the motor protein MCAK controls its structure and activity through a conformational switch'. Together they form a unique fingerprint.

Cite this