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 Rosenfeld, Anne Houdusse, Carolyn A. Moores

Research output: Contribution to journalArticle

11 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Kinesin
Microtubules
Nucleotides
Cryoelectron Microscopy
Dissection
Anaphase
Nucleotide Motifs
Docks
Cytokinesis
Metaphase
Electron microscopy
Adenosine Triphosphatases
Conformations
Assays
Neck
Adenosine Triphosphate

ASJC Scopus subject areas

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

Cite this

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

The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry. / Atherton, Joseph; Yu, I. Mei; Cook, Alexander; Muretta, Joseph M.; Joseph, Agnel; Major, Jennifer; Sourigues, Yannick; Clause, Jeffrey; Topf, Maya; Rosenfeld, Steven; Houdusse, Anne; Moores, Carolyn A.

In: eLife, Vol. 6, A27793, 11.08.2017.

Research output: Contribution to journalArticle

Atherton, J, Yu, IM, Cook, A, Muretta, JM, Joseph, A, Major, J, Sourigues, Y, Clause, J, Topf, M, Rosenfeld, S, Houdusse, A & Moores, CA 2017, 'The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry', eLife, vol. 6, A27793. https://doi.org/10.7554/eLife.27793
Atherton J, Yu IM, Cook A, Muretta JM, Joseph A, Major J et al. The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry. eLife. 2017 Aug 11;6. A27793. https://doi.org/10.7554/eLife.27793
Atherton, Joseph ; Yu, I. Mei ; Cook, Alexander ; Muretta, Joseph M. ; Joseph, Agnel ; Major, Jennifer ; Sourigues, Yannick ; Clause, Jeffrey ; Topf, Maya ; Rosenfeld, Steven ; Houdusse, Anne ; Moores, Carolyn A. / The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry. In: eLife. 2017 ; Vol. 6.
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