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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
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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. |
format | Online Article Text |
id | pubmed-5602324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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