8U70

Crystal structure of malaria transmission-blocking anti-Pfs48/45 antibody RUPA-58.

Summary for 8U70

• Entry DOI: 10.2210/pdb8u70/pdb
• Descriptor: Antibody RUPA-58 Kappa chain, Antibody RUPA-58 Heavy chain (2 entities in total)
• Functional Keywords: pfs48/45, human transmission-blocking antibodies, malaria, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 287318.91

Authors

Hailemariam, S.,Ivanochko, D.,Julien, J.P. (deposition date: 2023-09-14, release date: 2024-09-18, Last modification date: 2025-08-20)

Primary citation

Kucharska, I.,Ivanochko, D.,Hailemariam, S.,Inklaar, M.R.,Kim, H.R.,Teelen, K.,Stoter, R.,van de Vegte-Bolmer, M.,van Gemert, G.J.,Semesi, A.,McLeod, B.,Ki, A.,Lee, W.K.,Rubinstein, J.L.,Jore, M.M.,Julien, J.P.
Structural elucidation of full-length Pfs48/45 in complex with potent monoclonal antibodies isolated from a naturally exposed individual.
Nat.Struct.Mol.Biol., 32:1396-1407, 2025

PubMed Abstract: Biomedical interventions that block the transmission of Plasmodium falciparum (Pf) from humans to mosquitoes may be critical for malaria elimination. Pfs48/45, a gamete-surface protein essential for Pf development in the mosquito midgut, is a target of clinical-stage transmission-blocking vaccines and monoclonal antibodies (mAbs) that disrupt Pf transmission to mosquitoes. Antibodies directed to domain 3 of Pfs48/45 have been structurally and functionally described; however, in-depth information about other inhibitory epitopes on Pfs48/45 is currently limited. Here, we present a cryo-electron microscopy structure of full-length Pfs48/45 in complex with potent human mAbs targeting all three domains. Our data indicate that although Pfs48/45 domains 1 and 2 are rigidly coupled, there is substantial conformational flexibility between domains 2 and 3. Characterization of mAbs against domain 1 revealed the presence of a conformational epitope class that is largely conserved across Pf field isolates and is associated with recognition by potent antibodies. Our study provides insights into epitopes across full-length Pfs48/45 and has implications for the design of next-generation malaria interventions.

PubMed: 40404982
DOI: 10.1038/s41594-025-01532-6

Experimental method

X-RAY DIFFRACTION (3.09 Å)