Proteomics

Dataset Information

0

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

ABSTRACT: Plasmodium falciparum Pfs230 and Pfs48/45 are the leading candidates for malaria transmission-blocking vaccines. However, it remains unknown how the two interact and if additional domains in Pfs230 are potential vaccine candidates. Here we report a 3.36 Å resolution cryo-electron microscopy structure of the endogenous Pfs230-Pfs48/45 complex. We show that Pfs48/45 interacts with Pfs230 domains 13 and 14, which are distinct from domains included in current Pfs230 vaccine immunogens. Using a transgenic line with a domain 13 to 14 deletion, we show that these domains are essential for Pfs230 localization on the gamete surface. Nanobodies against these domains inhibit Pfs230-Pfs48/45 complex formation, reduce transmission and structural analyses reveal their binding epitopes. Pfs230 domains 13 and 14 are targets of naturally acquired immunity and when delivered as mRNA-LNP vaccines induced potent immune responses. Our comprehensive structural insights on a core P. falciparum fertilization complex guide the design of novel transmission-blocking vaccine candidates against malaria.

INSTRUMENT(S):

ORGANISM(S): Plasmodium Falciparum (isolate 3d7)

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: Laura Dagley  

LAB HEAD: Wai-Hong Tham

PROVIDER: PXD060667 | Pride | 2025-08-08

REPOSITORIES: Pride

Json Xml

Dataset's files

Source:
Action DRS
P4374_01.zip Other
P4374_02.zip Other
P4374_03.zip Other
P4374_04.zip Other
P4374_txt.zip Other
Items per page:
1 - 5 of 8
altmetric image

Publications

Malaria parasite fertilization occurs in the midgut of a female <i>Anopheles</i> mosquito. Blocking fertilization within the mosquito can prevent malaria transmission. <i>Plasmodium falciparum</i> 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 interact  ...[more]

Similar Datasets

Proteomics FLAG-tag based co-immunoprecipitation of the Plasmodium falciparum Pfs230:Pfs48/45 complex
2025-10-09 | PXD060716 | Pride
Proteomics Quantitative proteomics of the 2016 WHO Neisseria gonorrhoeae reference strains identifies vaccine candidates and antimicrobial resistance signatures.
2018-12-19 | PXD008412 | Pride
Proteomics Exoproteomic analysis of two MLST clade 2 strains of Clostridioides difficile from Latin America
2021-07-01 | PXD026218 | Pride
Proteomics Quantitative Proteomics of Enriched Esophageal and Gut Tissues from the Human Blood Fluke Schistosoma mansoni
2019-12-11 | PXD014872 | Pride
Proteomics Characterization of pathogenic Candida glabrata and their effectiveness against systemic candidiasis in BALB/c mice
2023-03-11 | PXD032928 | Pride
Transcriptomics Gene expression profiling of rhesus macaques vaccinated with ALVAC-SIVgpe DNA + SIVgp120 protein subunit and unvaccinated controls after challenge with SIVmac251 - 3 wks post-infection
2013-03-01 | E-GEOD-37311 | biostudies-arrayexpress
Transcriptomics Gene expression profiling of rhesus macaques vaccinated with ALVAC-SIVgpe DNA + SIVgp120 protein subunit and unvaccinated controls after challenge with SIVmac251 - 11 wks post-infection
2013-03-01 | E-GEOD-37312 | biostudies-arrayexpress
Proteomics Proteomic identification of Galectin-11 and 14 ligands from Haemonchus contortus
2018-02-28 | PXD008435 | Pride
Genomics Prototype LNP-mRNA vaccine candidates [SC_RNAseq]
| PRJNA853803 | ENA
Transcriptomics Gene expression profiling of rhesus macaques vaccinated with ALVAC-SIVgpe DNA + SIVgp120 protein subunit and unvaccinated controls after challenge with SIVmac251 - 3 wks post-infection
2013-03-01 | GSE37311 | GEO