6O2B

Crystal structure of 4493 Fab in complex with circumsporozoite protein DND and anti-kappa VHH domain

6O2B の概要

• エントリーDOI: 10.2210/pdb6o2b/pdb
• 関連するPDBエントリー: 6O23 6O24 6O25 6O26 6O27 6O28 6O29 6O2A
• 分子名称: 4493 Fab heavy chain, 4493 Kappa light chain, Anti-kappa VHH domain, ... (7 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: 16
• 化学式量合計: 239915.41

構造登録者

Scally, S.W.,Bosch, A.,Prieto, K.,Murugan, R.,Wardemann, H.,Julien, J.P. (登録日: 2019-02-22, 公開日: 2020-07-01, 最終更新日: 2024-10-16)

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 (2.1 Å)