6ULF

Crystal structure of 4498 Fab in complex with circumsporozoite protein NDN3 and anti-Kappa VHH domain

Summary for 6ULF

• Entry DOI: 10.2210/pdb6ulf/pdb
• Descriptor: 4498 Fab heavy chain, 4498 Fab light chain, anti Kappa VHH domain, ... (5 entities in total)
• Functional Keywords: malaria, antibody, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 60684.07

Authors

Thai, E.,Scally, S.W.,Prieto, K.,Murugan, R.,Wardemann, H.,Julien, J.P. (deposition date: 2019-10-07, release date: 2020-06-17, Last modification date: 2024-10-16)

Primary citation

Murugan, R.,Scally, S.W.,Costa, G.,Mustafa, G.,Thai, E.,Decker, T.,Bosch, A.,Prieto, K.,Levashina, E.A.,Julien, J.P.,Wardemann, H.
Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs.
Nat. Med., 26:1135-1145, 2020

PubMed Abstract: The circumsporozoite protein of the human malaria parasite Plasmodium falciparum (PfCSP) is the main target of antibodies that prevent the infection and disease, as shown in animal models. However, the limited efficacy of the PfCSP-based vaccine RTS,S calls for a better understanding of the mechanisms driving the development of the most potent human PfCSP antibodies and identification of their target epitopes. By characterizing 200 human monoclonal PfCSP antibodies induced by sporozoite immunization, we establish that the most potent antibodies bind around a conserved (N/D)PNANPN(V/A) core. High antibody affinity to the core correlates with protection from parasitemia in mice and evolves around the recognition of NANP motifs. The data suggest that the rational design of a next-generation PfCSP vaccine that elicits high-affinity antibody responses against the core epitope will promote the induction of protective humoral immune responses.

PubMed: 32451496
DOI: 10.1038/s41591-020-0881-9

Experimental method

X-RAY DIFFRACTION (1.7 Å)