Cryo-EM structure of a microtubule-bound parasite kinesin motor and implications for its mechanism and inhibition.

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 classic

SUBMITTER: Cook AD 

PROVIDER: S-EPMC8526983 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature