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A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin
The activity of a kinesin is largely determined by the approximately 350 residue motor domain, and this region alone is sufficient to classify a kinesin as a member of a particular family. The kinesin-13 family are a group of microtubule depolymerizing kinesins and are vital regulators of microtubul...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428548/ https://www.ncbi.nlm.nih.gov/pubmed/36043268 http://dx.doi.org/10.1098/rsob.220133 |
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author | Belsham, Hannah R. Alghamdi, Hanan M. Dave, Nikita Rathbone, Alexandra J. Wickstead, Bill Friel, Claire T. |
author_facet | Belsham, Hannah R. Alghamdi, Hanan M. Dave, Nikita Rathbone, Alexandra J. Wickstead, Bill Friel, Claire T. |
author_sort | Belsham, Hannah R. |
collection | PubMed |
description | The activity of a kinesin is largely determined by the approximately 350 residue motor domain, and this region alone is sufficient to classify a kinesin as a member of a particular family. The kinesin-13 family are a group of microtubule depolymerizing kinesins and are vital regulators of microtubule length. Kinesin-13s are critical to spindle assembly and chromosome segregation in both mitotic and meiotic cell division and play crucial roles in cilium length control and neuronal development. To better understand the evolution of microtubule depolymerization activity, we created a synthetic ancestral kinesin-13 motor domain. This phylogenetically inferred ancestral motor domain is the sequence predicted to have existed in the common ancestor of the kinesin-13 family. Here we show that the ancestral kinesin-13 motor depolymerizes stabilized microtubules faster than any previously tested depolymerase. This potent activity is more than an order of magnitude faster than the most highly studied kinesin-13, MCAK and allows the ancestral kinesin-13 to depolymerize doubly stabilized microtubules and cause internal breaks within microtubules. These data suggest that the ancestor of the kinesin-13 family was a ‘super depolymerizer’ and that members of the kinesin-13 family have evolved away from this extreme depolymerizing activity to provide more controlled microtubule depolymerization activity in extant cells. |
format | Online Article Text |
id | pubmed-9428548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-94285482022-09-01 A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin Belsham, Hannah R. Alghamdi, Hanan M. Dave, Nikita Rathbone, Alexandra J. Wickstead, Bill Friel, Claire T. Open Biol Research The activity of a kinesin is largely determined by the approximately 350 residue motor domain, and this region alone is sufficient to classify a kinesin as a member of a particular family. The kinesin-13 family are a group of microtubule depolymerizing kinesins and are vital regulators of microtubule length. Kinesin-13s are critical to spindle assembly and chromosome segregation in both mitotic and meiotic cell division and play crucial roles in cilium length control and neuronal development. To better understand the evolution of microtubule depolymerization activity, we created a synthetic ancestral kinesin-13 motor domain. This phylogenetically inferred ancestral motor domain is the sequence predicted to have existed in the common ancestor of the kinesin-13 family. Here we show that the ancestral kinesin-13 motor depolymerizes stabilized microtubules faster than any previously tested depolymerase. This potent activity is more than an order of magnitude faster than the most highly studied kinesin-13, MCAK and allows the ancestral kinesin-13 to depolymerize doubly stabilized microtubules and cause internal breaks within microtubules. These data suggest that the ancestor of the kinesin-13 family was a ‘super depolymerizer’ and that members of the kinesin-13 family have evolved away from this extreme depolymerizing activity to provide more controlled microtubule depolymerization activity in extant cells. The Royal Society 2022-08-31 /pmc/articles/PMC9428548/ /pubmed/36043268 http://dx.doi.org/10.1098/rsob.220133 Text en © 2022 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Research Belsham, Hannah R. Alghamdi, Hanan M. Dave, Nikita Rathbone, Alexandra J. Wickstead, Bill Friel, Claire T. A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin |
title | A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin |
title_full | A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin |
title_fullStr | A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin |
title_full_unstemmed | A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin |
title_short | A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin |
title_sort | synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428548/ https://www.ncbi.nlm.nih.gov/pubmed/36043268 http://dx.doi.org/10.1098/rsob.220133 |
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