5mm4
Ustilago maydis kinesin-5 motor domain in the AMPPNP state bound to microtubulesUstilago maydis kinesin-5 motor domain in the AMPPNP state bound to microtubules
Structural highlights
FunctionPublication Abstract from PubMedIn 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 alpha-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. Cryo-EM structure of the Ustilago maydis kinesin-5 motor domain bound to microtubules.,von Loeffelholz O, Moores CA J Struct Biol. 2019 Jul 6. pii: S1047-8477(19)30139-X. doi:, 10.1016/j.jsb.2019.07.003. PMID:31288039[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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