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| Title | Cryo-EM structure of the Ustilago maydis kinesin-5 motor domain bound to microtubules. |
|---|---|
| Journal, issue, pages | J Struct Biol, Vol. 207, Issue 3, Page 312-316, Year 2019 |
| Publish date | Sep 1, 2019 |
 Authors | Ottilie von Loeffelholz / Carolyn Ann Moores /  |
| PubMed 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 ...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. |
 External links | J Struct Biol / PubMed:31288039 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.5 - 5.1 Å |
| Structure data | |
| Chemicals |  ChemComp-MG:  ChemComp-ANP:  ChemComp-GTP:  ChemComp-TA1:  ChemComp-GDP: |
| Source |
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 Keywords |  MOTOR PROTEIN / Ustilago maydis / kinesin-5 |
