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Updated: Jan 15, 2026
Preparing Lamellae from Vitreous Biological Samples Using a Dual-Beam Scanning Electron Microscope for Cryo-Electron Tomography
Published on: August 5, 2021
Cryo-EM structure of endogenous Pfs230:Pfs48/45 complex with six antibodies reveals mechanisms of malaria
Ezra T Bekkering1, Randy Yoo2, Sophia Hailemariam2
1Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
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.
Insights
The Pfs230:Pfs48/45 complex is key for malaria vaccines. Cryo-EM revealed its structure bound to antibodies, showing membrane retention isn't vital for blocking transmission.
Area of Science:
- Structural Biology
- Immunology
- Parasitology
Background:
- The Pfs230:Pfs48/45 complex is crucial for malaria transmission-blocking vaccine candidates.
- Limited knowledge exists regarding the molecular assembly of this complex.
Purpose of the Study:
- To elucidate the structure of the endogenous Pfs230:Pfs48/45 complex bound to transmission-blocking antibodies.
- To understand the molecular mechanisms underlying malaria transmission blocking.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was employed to determine the structure.
- Analysis of antibody binding sites and complex interactions.
Main Results:
- The structure revealed Pfs230 domain clusters and a disk-like Pfs48/45 structure.
- A Pfs230 C-terminal peptide mediated membrane retention, which was not essential for blocking transmission.
- Conserved epitopes were identified, providing insights into antibody mechanisms.
Conclusions:
- The antibody-bound Pfs230:Pfs48/45 structure enhances molecular understanding of the complex.
- Findings inform the development of next-generation Plasmodium falciparum transmission-blocking interventions.
