The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry

Joseph Atherton, I. Mei Yu, Alexander Cook, Joseph M. Muretta, Agnel Joseph, Jennifer Major, Yannick Sourigues, Jeffrey Clause, Maya Topf, Steven S. Rosenfeld, Anne Houdusse, Carolyn A. Moores

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

MKLP2, a kinesin-6, has critical roles during the metaphase-anaphase transition and cytokinesis. Its motor domain contains conserved nucleotide binding motifs, but is divergent in sequence (~35% identity) and size (~40% larger) compared to other kinesins. Using cryo-electron microscopy and biophysical assays, we have undertaken a mechanochemical dissection of the microtubule-bound MKLP2 motor domain during its ATPase cycle, and show that many facets of its mechanism are distinct from other kinesins. While the MKLP2 neck-linker is directed towards the microtubule plus-end in an ATP-like state, it does not fully dock along the motor domain. Furthermore, the footprint of the MKLP2 motor domain on the MT surface is altered compared to motile kinesins, and enhanced by kinesin-6-specific sequences. The conformation of the highly extended loop6 insertion characteristic of kinesin-6s is nucleotide-independent and does not contact the MT surface. Our results emphasize the role of family-specific insertions in modulating kinesin motor function.

Original languageEnglish (US)
Article numberA27793
JournaleLife
Volume6
DOIs
StatePublished - Aug 11 2017

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Atherton, J., Yu, I. M., Cook, A., Muretta, J. M., Joseph, A., Major, J., Sourigues, Y., Clause, J., Topf, M., Rosenfeld, S. S., Houdusse, A., & Moores, C. A. (2017). The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry. eLife, 6, [A27793]. https://doi.org/10.7554/eLife.27793