Cryo-EM structure of endogenous Plasmodium falciparum Pfs230 and Pfs48/45 fertilization complex

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dc.contributor.authorDietrich, Melanie H.en
dc.contributor.authorChmielewski, Jillen
dc.contributor.authorChan, Li-Jinen
dc.contributor.authorTan, Li Lynnen
dc.contributor.authorAdair, Amyen
dc.contributor.authorLyons, Frankie M.T.en
dc.contributor.authorGabriela, Mikhaen
dc.contributor.authorLopaticki, Sashen
dc.contributor.authorDite, Toby Aen
dc.contributor.authorDagley, Laura F.en
dc.contributor.authorPazzagli, Luciaen
dc.contributor.authorGupta, Priyaen
dc.contributor.authorKamil, Mohden
dc.contributor.authorVaughan, Ashley M.en
dc.contributor.authorRojrung, Rattanapornen
dc.contributor.authorAbraham, Anjuen
dc.contributor.authorMazhari, Raminen
dc.contributor.authorLongley, Rheaen
dc.contributor.authorZeglinski, Kathleenen
dc.contributor.authorGouil, Quentinen
dc.contributor.authorMueller, Ivoen
dc.contributor.authorFabb, Stewart Aen
dc.contributor.authorShandre-Mugan, Rekhaen
dc.contributor.authorPouton, Colin Wen
dc.contributor.authorGlukhova, Alisaen
dc.contributor.authorShakeel, Shabihen
dc.contributor.authorTham, Wai Hongen
dc.date.accessioned2025-12-17T15:41:37Z
dc.date.available2025-12-17T15:41:37Z
dc.date.issued2025-07-31en
dc.description.abstractMalaria parasite fertilization occurs in the midgut of a female Anopheles mosquito. Blocking fertilization within the mosquito can prevent malaria transmission. Plasmodium falciparum Pfs230 and Pfs48/45 are critical for male fertility and transmission of the malaria parasite. They form a core fertilization complex, but it is unknown how they interact. We determined a cryo–electron microscopy structure of endogenous Pfs230-Pfs48/45 complex showing that Pfs48/45 interacts with Pfs230 domains 13 and 14. Transgenic parasite lines with these domains removed were defective in Pfs230 gamete localization and showed reduced oocyst formation. Nanobodies against domains 13 and 14 inhibited Pfs230-Pfs48/45 complex formation, reduced transmission and structural analyses revealed their epitopes. These Pfs230 domains were targets of naturally acquired immunity and immune sera from mRNA–lipid nanoparticle immunizations blocked parasite transmission.en
dc.description.sponsorshipNational Health and Medical Research Council grant GNT2016908 (W.-H.T.); National Health and Medical Research Council grant GNT2001385 (W.-H.T.); National Health and Medical Research Council grantGNT2007996 (Q.G.); National Health and Medical Research Council grant GNT1173210(R.J.L.); National Health and Medical Research Council grant GNT2016827 (S.S.); Medical Research Future Fund grant MRFCT100006 (C.W.P.); CSL Centenary Fellow (A.G.); Victorian State Government Operational Infrastructure Support and National Health and Medical Research Council Independent Research Institute Infrastructure Support Schemeen
dc.description.statusPeer-revieweden
dc.format.extent16en
dc.identifier.issn0036-8075en
dc.identifier.scopus105015504901en
dc.identifier.urihttps://hdl.handle.net/1885/733796161
dc.language.isoenen
dc.provenancehttps://openpolicyfinder.jisc.ac.uk/id/publication/11114..."The Accepted Version can be archived in a Non-Commercial Institutional Repository. " from Open Policy Finder site (as at 22/09/2025) This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in [Science] on [31 July 2025]; DOI: [https://dx.doi.org/10.1126/science.ady0241].en
dc.rights© 2025 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Worksen
dc.sourceScienceen
dc.titleCryo-EM structure of endogenous Plasmodium falciparum Pfs230 and Pfs48/45 fertilization complexen
dc.typeJournal articleen
dspace.entity.typePublicationen
local.bibliographicCitation.lastpage16en
local.bibliographicCitation.startpage1en
local.contributor.affiliationDietrich, Melanie H.; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationChmielewski, Jill; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationChan, Li-Jin; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationTan, Li Lynn; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationAdair, Amy; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationLyons, Frankie M.T.; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationGabriela, Mikha; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationLopaticki, Sash; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationDite, Toby A; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationDagley, Laura F.; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationPazzagli, Lucia; Seattle Children's Research Instituteen
local.contributor.affiliationGupta, Priya; Seattle Children's Research Instituteen
local.contributor.affiliationKamil, Mohd; Seattle Children's Research Instituteen
local.contributor.affiliationVaughan, Ashley M.; Seattle Biomedical Research Instituteen
local.contributor.affiliationRojrung, Rattanaporn; Ehime Universityen
local.contributor.affiliationAbraham, Anju; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationMazhari, Ramin; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationLongley, Rhea; University of Tasmaniaen
local.contributor.affiliationZeglinski, Kathleen; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationGouil, Quentin; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationMueller, Ivo; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationFabb, Stewart A; Monash Institute of Pharmaceutical Sciencesen
local.contributor.affiliationShandre-Mugan, Rekha; Monash Institute of Pharmaceutical Sciencesen
local.contributor.affiliationPouton, Colin W; Monash Universityen
local.contributor.affiliationGlukhova, Alisa; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationShakeel, Shabih; Walter and Eliza Hall Institute of Medical Researchen
local.contributor.affiliationTham, Wai Hong; Division of Biomedical Science & Biochemistry, Research School of Biology, ANU College of Science and Medicine, The Australian National Universityen
local.identifier.citationvolume389en
local.identifier.doi10.1126/science.ady0241en
local.identifier.purefde05f7c-38a9-442d-888f-551ca148233een
local.identifier.urlhttps://www.scopus.com/pages/publications/105015504901en
local.type.statusE-pub ahead of printen

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