9N5H

Endogenous Pfs230D1-6 in complex with RUPA-97, LMIV230-01, and 2A2 Fab domains

Summary for 9N5H

• Entry DOI: 10.2210/pdb9n5h/pdb
• EMDB information: 48921
• Descriptor: Gametocyte surface protein P230, 2A2 Heavy Chain, 2A2 Kappa Chain, ... (7 entities in total)
• Functional Keywords: 6-cys, antibody, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 7
• Total formula weight: 505104.87

Authors

Heide, F.,Yoo, R.,Ivanochko, D.,Hailemariam, S.,Bekkering, E.,Julien, J.P. (deposition date: 2025-02-04, release date: 2025-10-15, Last modification date: 2025-10-22)

Primary citation

Bekkering, E.T.,Yoo, R.,Hailemariam, S.,Heide, F.,Ivanochko, D.,Jackman, M.,Proellochs, N.I.,Stoter, R.,van Gemert, G.J.,Maeda, A.,Yuguchi, T.,Wanders, O.T.,van Daalen, R.C.,Inklaar, M.R.,Andrade, C.M.,Jansen, P.W.T.C.,Vermeulen, M.,Bousema, T.,Takashima, E.,Rubinstein, J.L.,Kooij, T.W.A.,Jore, M.M.,Julien, J.P.
Structure of endogenous Pfs230:Pfs48/45 in complex with potent malaria transmission-blocking antibodies.
Biorxiv, 2025

PubMed 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 cryogenic electron microscopy to elucidate the structure of the endogenous Pfs230:Pfs48/45 complex bound to six potent transmission-blocking antibodies. Pfs230 consists of multiple domain clusters rigidified by interactions mediated through insertion domains. Membrane-anchored Pfs48/45 forms a disc-like structure and interacts with a short C-terminal peptide on Pfs230 that is critical for Pfs230 membrane-retention . Interestingly, membrane retention through this interaction is 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 identify conserved epitopes on the Pfs230:Pfs48/45 complex and provides a structural paradigm for complement-dependent activity of Pfs230-targeting antibodies. Altogether, the antibody-bound Pfs230:Pfs48/45 structure presented improves our molecular understanding of this biological complex, informing the development of next-generation transmission-blocking interventions.

PubMed: 39990443
DOI: 10.1101/2025.02.14.638310

Experimental method

ELECTRON MICROSCOPY (3.6 Å)