biostudies-literatureUnknownBekkering ETDutch Research Council (NWO)NIGMS NIH HHSThe 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 <i>in vivo</i>. 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 antbioRxiv : the preprint server for biology2025.02.14.638310https://www.ebi.ac.uk/biostudies/studies/S-EPMC11844449biostudies-literatureStructure of endogenous Pfs230:Pfs48/45 in complex with potent malaria transmission-blocking antibodies.PMC11844449R01 GM129325VI.Veni.222.381Jansen PWTCTakashima EHeide FJore MMProellochs NIBekkering ETMaeda AIvanochko DVermeulen MYuguchi TJackman MInklaar MRYoo Rvan Daalen RCRubinstein JLJulien JPStoter RWanders OTvan Gemert GJAndrade CMBousema THailemariam SKooij TWAfalseStructure of endogenous Pfs230:Pfs48/45 in complex with potent malaria transmission-blocking antibodies.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 <i>in vivo</i>. 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 ant2025-01-01T00:00:00Z2025 Jun2026-07-03T03:25:40.123Z2025-04-07T07:50:03.757ZS-EPMC118444493999044310.1101/2025.02.14.638310