7NBA

Plasmodium falciparum kinesin-5 motor domain bound to AMPPNP, complexed with 14 protofilament microtubule.

7NBA の概要

• エントリーDOI: 10.2210/pdb7nba/pdb
• EMDBエントリー: 12257 12258
• 分子名称: Tubulin alpha-1B chain, Tubulin beta chain, Kinesin motor domain-containing protein,Kinesin motor domain-containing protein, ... (7 entities in total)
• 機能のキーワード: cytoskeleton, motor protein, mitotic
• 由来する生物種: Plasmodium falciparum (isolate NF54); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 148645.83

構造登録者

Cook, A.D.,Roberts, A.,Atherton, J.,Tewari, R.,Topf, M.,Moores, C.A. (登録日: 2021-01-25, 公開日: 2021-10-13, 最終更新日: 2024-07-10)

主引用文献

Cook, A.D.,Roberts, A.J.,Atherton, J.,Tewari, R.,Topf, M.,Moores, C.A.
Cryo-EM structure of a microtubule-bound parasite kinesin motor and implications for its mechanism and inhibition.
J.Biol.Chem., 297:101063-101063, 2021

PubMed Abstract: 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.

PubMed: 34375637
DOI: 10.1016/j.jbc.2021.101063

実験手法

ELECTRON MICROSCOPY (4 Å)