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-Structure paper
タイトル | Cryo-EM structure of the Ustilago maydis kinesin-5 motor domain bound to microtubules. |
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ジャーナル・号・ページ | J Struct Biol, Vol. 207, Issue 3, Page 312-316, Year 2019 |
掲載日 | 2019年9月1日 |
著者 | Ottilie von Loeffelholz / Carolyn Ann Moores / |
PubMed 要旨 | 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. |
リンク | J Struct Biol / PubMed:31288039 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.5 - 5.1 Å |
構造データ | |
化合物 | ChemComp-MG: ChemComp-ANP: ChemComp-GTP: ChemComp-TA1: ChemComp-GDP: |
由来 |
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キーワード | MOTOR PROTEIN / Ustilago maydis / kinesin-5 |