Cryo-EM structure of endogenous Plasmodium falciparum Pfs230 and Pfs48/45 fertilization complex
2
Issued Date
2025-09-11
Resource Type
ISSN
00368075
eISSN
10959203
Scopus ID
2-s2.0-105015504901
Pubmed ID
40743371
Journal Title
Science
Volume
389
Issue
6765
Rights Holder(s)
SCOPUS
Bibliographic Citation
Science Vol.389 No.6765 (2025)
Suggested Citation
Dietrich M.H., Chmielewski J., Chan L.J., Tan L.L., Adair A., Lyons F.M.T., Gabriela M., Lopaticki S., Dite T.A., Dagley L.F., Pazzagli L., Gupta P., Kamil M., Vaughan A.M., Rojrung R., Abraham A., Mazhari R., Longley R.J., Zeglinski K., Gouil Q., Mueller I., Fabb S.A., Shandre-Mugan R., Pouton C.W., Glukhova A., Shakeel S., Tham W.H. Cryo-EM structure of endogenous Plasmodium falciparum Pfs230 and Pfs48/45 fertilization complex. Science Vol.389 No.6765 (2025). doi:10.1126/science.ady0241 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112185
Title
Cryo-EM structure of endogenous Plasmodium falciparum Pfs230 and Pfs48/45 fertilization complex
Author(s)
Dietrich M.H.
Chmielewski J.
Chan L.J.
Tan L.L.
Adair A.
Lyons F.M.T.
Gabriela M.
Lopaticki S.
Dite T.A.
Dagley L.F.
Pazzagli L.
Gupta P.
Kamil M.
Vaughan A.M.
Rojrung R.
Abraham A.
Mazhari R.
Longley R.J.
Zeglinski K.
Gouil Q.
Mueller I.
Fabb S.A.
Shandre-Mugan R.
Pouton C.W.
Glukhova A.
Shakeel S.
Tham W.H.
Chmielewski J.
Chan L.J.
Tan L.L.
Adair A.
Lyons F.M.T.
Gabriela M.
Lopaticki S.
Dite T.A.
Dagley L.F.
Pazzagli L.
Gupta P.
Kamil M.
Vaughan A.M.
Rojrung R.
Abraham A.
Mazhari R.
Longley R.J.
Zeglinski K.
Gouil Q.
Mueller I.
Fabb S.A.
Shandre-Mugan R.
Pouton C.W.
Glukhova A.
Shakeel S.
Tham W.H.
Author's Affiliation
Shanghai Jiao Tong University
University of Melbourne
Monash University
University of Washington School of Medicine
Ehime University
Walter and Eliza Hall Institute of Medical Research
ANU Research School of Biology
Faculty of Tropical Medicine, Mahidol University
The Peter Doherty Institute for Infection and Immunity
Olivia Newton-John Cancer Research Institute
Seattle Children’s Research Institute
University of Melbourne
Monash University
University of Washington School of Medicine
Ehime University
Walter and Eliza Hall Institute of Medical Research
ANU Research School of Biology
Faculty of Tropical Medicine, Mahidol University
The Peter Doherty Institute for Infection and Immunity
Olivia Newton-John Cancer Research Institute
Seattle Children’s Research Institute
Corresponding Author(s)
Other Contributor(s)
Abstract
Malaria 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 proteins 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 the 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 and reduced transmission, and structural analyses revealed their epitopes. These Pfs230 domains were targets of naturally acquired immunity and immune sera from messenger RNA lipid nanoparticle immunizations blocked parasite transmission.