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The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry

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 biophysic...

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Autores principales: Atherton, Joseph, Yu, I-Mei, Cook, Alexander, Muretta, Joseph M, Joseph, Agnel, Major, Jennifer, Sourigues, Yannick, Clause, Jeffrey, Topf, Maya, Rosenfeld, Steven S, Houdusse, Anne, Moores, Carolyn A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602324/
https://www.ncbi.nlm.nih.gov/pubmed/28826477
http://dx.doi.org/10.7554/eLife.27793
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author Atherton, Joseph
Yu, I-Mei
Cook, Alexander
Muretta, Joseph M
Joseph, Agnel
Major, Jennifer
Sourigues, Yannick
Clause, Jeffrey
Topf, Maya
Rosenfeld, Steven S
Houdusse, Anne
Moores, Carolyn A
author_facet Atherton, Joseph
Yu, I-Mei
Cook, Alexander
Muretta, Joseph M
Joseph, Agnel
Major, Jennifer
Sourigues, Yannick
Clause, Jeffrey
Topf, Maya
Rosenfeld, Steven S
Houdusse, Anne
Moores, Carolyn A
author_sort Atherton, Joseph
collection PubMed
description 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.
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spelling pubmed-56023242017-09-19 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 S Houdusse, Anne Moores, Carolyn A eLife Structural Biology and Molecular Biophysics 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. eLife Sciences Publications, Ltd 2017-08-11 /pmc/articles/PMC5602324/ /pubmed/28826477 http://dx.doi.org/10.7554/eLife.27793 Text en © 2017, Atherton et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Structural Biology and Molecular Biophysics
Atherton, Joseph
Yu, I-Mei
Cook, Alexander
Muretta, Joseph M
Joseph, Agnel
Major, Jennifer
Sourigues, Yannick
Clause, Jeffrey
Topf, Maya
Rosenfeld, Steven S
Houdusse, Anne
Moores, Carolyn A
The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry
title The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry
title_full The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry
title_fullStr The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry
title_full_unstemmed The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry
title_short The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry
title_sort divergent mitotic kinesin mklp2 exhibits atypical structure and mechanochemistry
topic Structural Biology and Molecular Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602324/
https://www.ncbi.nlm.nih.gov/pubmed/28826477
http://dx.doi.org/10.7554/eLife.27793
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