Cryo-EM structure of the Ustilago maydis kinesin-5 motor domain bound to microtubules
von Loeffelholz, O. and Moores, Carolyn A. (2019) Cryo-EM structure of the Ustilago maydis kinesin-5 motor domain bound to microtubules. Journal of Structural Biology 207 (3), pp. 312-316. ISSN 1047-8477.
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Abstract
In many eukaryotes, kinesin-5 motors are essential for mitosis, and small molecules that inhibit human kinesin-5 disrupt cell division. To investigate whether fungal kinesin-5s could be targets for novel fungicides, we studied kinesin-5 from the pathogenic fungus Ustilago maydis. We used cryo-electron microscopy to determine the microtubule-bound structure of its motor domain with and without the N-terminal extension. The ATP-like conformations of the motor in the presence or absence of this N-terminus are very similar, suggesting this region is structurally disordered and does not directly influence the motor ATPase. The Ustilago maydis kinesin-5 motor domain adopts a canonical ATP-like conformation, thereby allowing the neck linker to bind along the motor domain towards the microtubule plus end. However, several insertions within this motor domain are structurally distinct. Loop2 forms a non-canonical interaction with α-tubulin, while loop8 may bridge between two adjacent protofilaments. Furthermore, loop5 - which in human kinesin-5 is involved in binding allosteric inhibitors - protrudes above the nucleotide binding site, revealing a distinct binding pocket for potential inhibitors. This work highlights fungal-specific elaborations of the kinesin-5 motor domain and provides the structural basis for future investigations of kinesins as targets for novel fungicides.
Metadata
Item Type: | Article |
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School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
Depositing User: | Administrator |
Date Deposited: | 08 Jul 2019 07:17 |
Last Modified: | 02 Aug 2023 17:52 |
URI: | https://eprints.bbk.ac.uk/id/eprint/28033 |
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