6VLN

Crystal structure of 4498 Fab in complex with circumsporozoite protein DND3 and anti-Kappa VHH domain

6VLN の概要

• エントリーDOI: 10.2210/pdb6vln/pdb
• 分子名称: 4498 Fab heavy chain, 4498 Fab light chain, anti Kappa VHH domain, ... (6 entities in total)
• 機能のキーワード: malaria, antibody, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 60805.20

構造登録者

Thai, E.,Scally, S.W.,Prieto, K.,Murugan, R.,Wardemann, H.,Julien, J.P. (登録日: 2020-01-24, 公開日: 2020-06-17, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.63 Å)