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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.

A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin Thumbnail


Authors

Hannah R. Belsham

Hanan M. Alghamdi

Nikita Dave

Alexandra J. Rathbone



Abstract

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.

Citation

Belsham, H. R., Alghamdi, H. M., Dave, N., Rathbone, A. J., Wickstead, B., & Friel, C. T. (2022). A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin. Open Biology, 12(8), Article 220133. https://doi.org/10.1098/rsob.220133

Journal Article Type Article
Acceptance Date Aug 8, 2022
Online Publication Date Aug 31, 2022
Publication Date 2022-08
Deposit Date Mar 12, 2024
Publicly Available Date Mar 14, 2024
Journal Open Biology
Publisher The Royal Society
Peer Reviewed Peer Reviewed
Volume 12
Issue 8
Article Number 220133
DOI https://doi.org/10.1098/rsob.220133
Keywords General Biochemistry, Genetics and Molecular Biology; Immunology; General Neuroscience
Public URL https://nottingham-repository.worktribe.com/output/10638241
Publisher URL https://royalsocietypublishing.org/doi/10.1098/rsob.220133

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