8EH5

Cryo-EM structure of L9 Fab in complex with rsCSP

8EH5 の概要

• エントリーDOI: 10.2210/pdb8eh5/pdb
• EMDBエントリー: 28135
• 分子名称: Circumsporozoite protein, L9 Heavy chain, L9 Light chain (3 entities in total)
• 機能のキーワード: pfcsp, malaria, antibody, immune system
• 由来する生物種: Plasmodium falciparum (malaria parasite P. falciparum); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 174581.42

構造登録者

Martin, G.M.,Ward, A.B. (登録日: 2022-09-13, 公開日: 2023-06-28, 最終更新日: 2024-11-13)

主引用文献

Martin, G.M.,Fernandez-Quintero, M.L.,Lee, W.H.,Pholcharee, T.,Eshun-Wilson, L.,Liedl, K.R.,Pancera, M.,Seder, R.A.,Wilson, I.A.,Ward, A.B.
Structural basis of epitope selectivity and potent protection from malaria by PfCSP antibody L9.
Nat Commun, 14:2815-2815, 2023

PubMed Abstract: A primary objective in malaria vaccine design is the generation of high-quality antibody responses against the circumsporozoite protein of the malaria parasite, Plasmodium falciparum (PfCSP). To enable rational antigen design, we solved a cryo-EM structure of the highly potent anti-PfCSP antibody L9 in complex with recombinant PfCSP. We found that L9 Fab binds multivalently to the minor (NPNV) repeat domain, which is stabilized by a unique set of affinity-matured homotypic, antibody-antibody contacts. Molecular dynamics simulations revealed a critical role of the L9 light chain in integrity of the homotypic interface, which likely impacts PfCSP affinity and protective efficacy. These findings reveal the molecular mechanism of the unique NPNV selectivity of L9 and emphasize the importance of anti-homotypic affinity maturation in protective immunity against P. falciparum.

PubMed: 37198165
DOI: 10.1038/s41467-023-38509-2

実験手法

ELECTRON MICROSCOPY (3.36 Å)