Structure of endogenous Pfs230:Pfs48/45 in complex with potent malaria transmission-blocking antibodies.

ABSTRACT: The Pfs230:Pfs48/45 complex forms the basis for leading malaria transmission-blocking vaccine candidates, yet little is known about its molecular assembly. Here, we used cryogenic electron microscopy to elucidate the structure of the endogenous Pfs230:Pfs48/45 complex bound to six potent transmission-blocking antibodies. Pfs230 consists of multiple domain clusters rigidified by interactions mediated through insertion domains. Membrane-anchored Pfs48/45 forms a disc-like structure and interacts with a short C-terminal peptide on Pfs230 that is critical for Pfs230 membrane-retention in vivo. Interestingly, membrane retention through this interaction is not essential for transmission to mosquitoes, suggesting that complex disruption is not a mode of action for transmission-blocking ant

SUBMITTER: Bekkering ET 

PROVIDER: S-EPMC11844449 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature