+検索条件
-Structure paper
タイトル | Cryo-EM structure of a microtubule-bound parasite kinesin motor and implications for its mechanism and inhibition. |
---|---|
ジャーナル・号・ページ | J Biol Chem, Vol. 297, Issue 5, Page 101063, Year 2021 |
掲載日 | 2021年8月8日 |
著者 | Alexander D Cook / Anthony J Roberts / Joseph Atherton / Rita Tewari / Maya Topf / Carolyn A Moores / |
PubMed 要旨 | Plasmodium parasites cause malaria and are responsible annually for hundreds of thousands of deaths. Kinesins are a superfamily of microtubule-dependent ATPases that play important roles in the ...Plasmodium parasites cause malaria and are responsible annually for hundreds of thousands of deaths. Kinesins are a superfamily of microtubule-dependent ATPases that play important roles in the parasite replicative machinery, which is a potential target for antiparasite drugs. Kinesin-5, a molecular motor that cross-links microtubules, is an established antimitotic target in other disease contexts, but its mechanism in Plasmodium falciparum is unclear. Here, we characterized P. falciparum kinesin-5 (PfK5) using cryo-EM to determine the motor's nucleotide-dependent microtubule-bound structure and introduced 3D classification of individual motors into our microtubule image processing pipeline to maximize our structural insights. Despite sequence divergence in PfK5, the motor exhibits classical kinesin mechanochemistry, including ATP-induced subdomain rearrangement and cover neck bundle formation, consistent with its plus-ended directed motility. We also observed that an insertion in loop5 of the PfK5 motor domain creates a different environment in the well-characterized human kinesin-5 drug-binding site. Our data reveal the possibility for selective inhibition of PfK5 and can be used to inform future exploration of Plasmodium kinesins as antiparasite targets. |
リンク | J Biol Chem / PubMed:34375637 / PubMed Central |
手法 | EM (らせん対称) |
解像度 | 4.0 - 4.4 Å |
構造データ | EMDB-12257, PDB-7nb8: EMDB-12258, PDB-7nba: |
化合物 | ChemComp-GTP: ChemComp-MG: ChemComp-G2P: ChemComp-ANP: |
由来 |
|
キーワード | MOTOR PROTEIN / Cytoskeleton / mitosis / mitotic |