The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry

eLife

Joseph M Muretta¹  Jennifer Major²  Steven S Rosenfeld²  Alexander Cook³  Agnel Joseph³  Joseph Atherton³  Carolyn A Moores³  Maya Topf³  Jeffrey Clause⁴  I-Mei Yu⁴  Anne Houdusse⁴  Yannick Sourigues⁴ 

[1] Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, United Sates;Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States;Institute of Structural and Molecular Biology, Birkbeck College, London, United Kingdom;Structural Motility, Institut Curie, Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Paris, France;

关键词: cryo-electron microscopy;    kinesins;    mechanochemistry;    microtubules;    mitosis;    ATPase;   

DOI  :  10.7554/eLife.27793

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown