Evidence map›Paper›PMID 41072404›Full record

ArticleImmunity2025

Cryo-EM structure of endogenous Pfs230:Pfs48/45 complex with six antibodies reveals mechanisms of malaria transmission-blocking activity.

Ezra T Bekkering, Randy Yoo, Sophia Hailemariam, Fabian Heide, Danton Ivanochko, Matthew Jackman, Nicholas I Proellochs, Rianne Stoter, Geert-Jan van Gemert, Ayana Maeda and 13 more

Abstract read
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In one paragraph

Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Ezra T BekkeringDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Randy YooProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Sophia HailemariamProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Fabian HeideProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Danton IvanochkoProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Matthew JackmanProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Nicholas I ProellochsDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Rianne StoterDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Geert-Jan van GemertDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Ayana MaedaDivision of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan.
Takaaki YuguchiDivision of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan.
Oscar T WandersDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Renate C van DaalenDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Maartje R InklaarDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Carolina M AndradeDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Pascal W T C JansenDepartment of Molecular Biology, Faculty of Science, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.
Michiel VermeulenDepartment of Molecular Biology, Faculty of Science, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands; Division of Molecular Genetics, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
Teun BousemaDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Eizo TakashimaDivision of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan.
John L RubinsteinProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Taco W A KooijDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Matthijs M JoreDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: matthijs.jore@radboudumc.nl.
Jean-Philippe JulienProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada. Electronic address: jean-philippe.julien@sickkids.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 cryo-electron microscopy to elucidate the structure of the endogenous Pfs230:Pfs48/45 complex bound to six transmission-blocking antibodies. Our structure revealed that Pfs230 consists of multiple domain clusters rigidified by interactions mediated through insertion domains. Membrane-anchored Pfs48/45 formed a disk-like structure, interacting with a short C-terminal peptide on Pfs230 that was critical for Pfs230 membrane-retention in vivo. Membrane retention through this interaction was 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 identified conserved epitopes on the Pfs230:Pfs48/45 complex and provided a structural paradigm for complement-dependent activity of Pfs230-targeting antibodies. Altogether, the antibody-bound Pfs230:Pfs48/45 structure improves our molecular understanding of this biological complex, informing the development of next-generation Plasmodium falciparum transmission-blocking interventions.

Indexed as

Antibodies, BlockingAntibodies, ProtozoanAntigens, ProtozoanMalaria, FalciparumPlasmodium falciparumProtozoan ProteinsAnimalsCryoelectron MicroscopyEpitopesHumansMalaria VaccinesMembrane GlycoproteinsProtein BindingAntibodies, BlockingAntibodies, ProtozoanAntigens, ProtozoanEpitopesMalaria VaccinesMembrane GlycoproteinsPfs230 antigen, Plasmodium falciparumpfs48-45 protein, Plasmodium falciparumProtozoan Proteinscryo-electron microscopymalariamonoclonal antibodiesPfs230Pfs48/45Plasmodium falciparumTBVtransmission-blocking antibodiestransmission-blocking vaccinestransmission-reducing activity

Identifiers

PMID41072404

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.