6BQB

MGG4 Fab in complex with peptide

6BQB の概要

• エントリーDOI: 10.2210/pdb6bqb/pdb
• 分子名称: MGG4 Fab light chain, MGG4 Fab heavy chain, N-terminal junction peptide, ... (5 entities in total)
• 機能のキーワード: human fab fragment peptide binding plasmodium falciparum circumsporozoite protein, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 49943.60

構造登録者

Oyen, D.,Tan, J.,Lanzavecchia, A.,Wilson, I.A. (登録日: 2017-11-27, 公開日: 2018-03-07, 最終更新日: 2018-04-25)

主引用文献

Tan, J.,Sack, B.K.,Oyen, D.,Zenklusen, I.,Piccoli, L.,Barbieri, S.,Foglierini, M.,Fregni, C.S.,Marcandalli, J.,Jongo, S.,Abdulla, S.,Perez, L.,Corradin, G.,Varani, L.,Sallusto, F.,Sim, B.K.L.,Hoffman, S.L.,Kappe, S.H.I.,Daubenberger, C.,Wilson, I.A.,Lanzavecchia, A.
A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein.
Nat. Med., 24:401-407, 2018

PubMed Abstract: Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been shown to be protective against malaria, but the features of the antibody response induced by this treatment remain unclear. To investigate this response in detail, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine and who were found to be protected from controlled human malaria infection with infectious homologous PfSPZs. All isolated IgG monoclonal antibodies bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in its N terminus, NANP-repeat region, and C terminus. Strikingly, the most effective antibodies, as determined in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and were encoded by VH3-30 or VH3-33 alleles that encode tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.

PubMed: 29554084
DOI: 10.1038/nm.4513

実験手法

X-RAY DIFFRACTION (1.769 Å)