9E7P

Pfs230 D13D14 in complex with nanobody W2812

Summary for 9E7P

• Entry DOI: 10.2210/pdb9e7p/pdb
• Descriptor: Nanobody W2812, Gametocyte surface protein P230, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: 6-cysteine protein, plasmodium falciparum, malaria transmission, nanobody, protein binding
• Biological source: Vicugna pacos; More
• Total number of polymer chains: 2
• Total formula weight: 48826.82

Authors

Dietrich, M.H.,Tan, L.L.,Tham, W.H. (deposition date: 2024-11-03, release date: 2025-07-30, Last modification date: 2025-09-24)

Primary 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, 389:eady0241-eady0241, 2025

PubMed Abstract: Malaria parasite fertilization occurs in the midgut of a female mosquito. Blocking fertilization within the mosquito can prevent malaria transmission. Pfs230 and Pfs48/45 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 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, reduced transmission and structural analyses revealed their epitopes. These Pfs230 domains were targets of naturally acquired immunity and immune sera from mRNA-lipid nanoparticle immunizations blocked parasite transmission.

PubMed: 40743371
DOI: 10.1126/science.ady0241

Experimental method

X-RAY DIFFRACTION (3.22 Å)