6B08

Crystal structure of Pfs25 in complex with the transmission blocking antibody 1276

Summary for 6B08

• Entry DOI: 10.2210/pdb6b08/pdb
• Related: 6AZZ
• Descriptor: 1276 antibody, heavy chain, 1276 antibody, light chain, Pfs25, ... (5 entities in total)
• Functional Keywords: transmission blocking vaccine, malaria, antibody, egf-like domain, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 67440.79

Authors

Scally, S.W.,McLeod, B.,Bosch, A.,King, C.R.,Julien, J.P. (deposition date: 2017-09-14, release date: 2017-11-15, Last modification date: 2024-10-23)

Primary citation

Scally, S.W.,McLeod, B.,Bosch, A.,Miura, K.,Liang, Q.,Carroll, S.,Reponen, S.,Nguyen, N.,Giladi, E.,Ramisch, S.,Yusibov, V.,Bradley, A.,Lemiale, F.,Schief, W.R.,Emerling, D.,Kellam, P.,King, C.R.,Julien, J.P.
Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.
Nat Commun, 8:1568-1568, 2017

PubMed Abstract: The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens.

PubMed: 29146922
DOI: 10.1038/s41467-017-01924-3

Experimental method

X-RAY DIFFRACTION (2.2 Å)