{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:25:52Z","timestamp":1790843152926,"version":"4.1.0"},"posted":{"date-parts":[[2025,2,15]]},"group-title":"Molecular Biology","reference-count":108,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:00:00Z","timestamp":1739577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,15]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  The Pfs230:Pfs48\/45 complex forms the basis for leading malaria transmission-blocking vaccine candidates, yet li]le 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\n                  <jats:italic>in vivo<\/jats:italic>\n                  . 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 antibodies. Analyses of Pfs48\/45-and Pfs230-targeted antibodies identify conserved epitopes on the Pfs230:Pfs48\/45 complex and provides a structural paradigm for complement-dependent activity of Pfs230-targeting antibodies. Altogether, the antibody-bound Pfs230:Pfs48\/45 structure presented improves our molecular understanding of this biological complex, informing the development of next-generation\n                  <jats:italic>Plasmodium falciparum<\/jats:italic>\n                  transmission-blocking interventions.\n                <\/jats:p>","DOI":"10.1101\/2025.02.14.638310","type":"posted-content","created":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T02:45:25Z","timestamp":1739673925000},"source":"Crossref","is-referenced-by-count":3,"title":["Structure of endogenous Pfs230:Pfs48\/45 in complex with potent malaria transmission-blocking antibodies"],"prefix":"10.64898","author":[{"given":"Ezra T.","family":"Bekkering","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-9039","authenticated-orcid":false,"given":"Randy","family":"Yoo","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada"},{"name":"Department of Biochemistry, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Hailemariam","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada"},{"name":"Department of Biochemistry, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Heide","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, 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C.","family":"van Daalen","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maartje R.","family":"Inklaar","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina M.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal W.T.C.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Science, Oncode Institute, Radboud University Nijmegen, Nijmegen, The 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