6WG2

Crystal structure of Fab239 in complex with NPNA4 peptide from circumsporozoite protein

6WG2 の概要

• エントリーDOI: 10.2210/pdb6wg2/pdb
• 分子名称: Fab239 heavy chain, Fab239 light chain, NPNA4 peptide, ... (4 entities in total)
• 機能のキーワード: malaria, sporozoite, circumsporozoite protein, 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: 5
• 化学式量合計: 97250.35

構造登録者

Pholcharee, T.,Oyen, D.,Wilson, I.A. (登録日: 2020-04-04, 公開日: 2020-07-29, 最終更新日: 2024-10-23)

主引用文献

Pholcharee, T.,Oyen, D.,Flores-Garcia, Y.,Gonzalez-Paez, G.,Han, Z.,Williams, K.L.,Volkmuth, W.,Emerling, D.,Locke, E.,Richter King, C.,Zavala, F.,Wilson, I.A.
Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum.
Nat Commun, 12:1063-1063, 2021

PubMed Abstract: The most advanced P. falciparum circumsporozoite protein-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable antibody responses. Here, we elucidate crystal structures, binding affinities and kinetics, and in vivo protection of eight anti-NANP antibodies derived from an RTS,S phase 2a trial and encoded by three different heavy-chain germline genes. The structures reinforce the importance of homotypic Fab-Fab interactions in protective antibodies and the overwhelmingly dominant preference for a germline-encoded aromatic residue for recognition of the NANP motif. In this study, antibody apparent affinity correlates best with protection in an in vivo mouse model, with the more potent antibodies also recognizing epitopes with repeating secondary structural motifs of type I β- and Asn pseudo 3 turns; such insights can be incorporated into design of more effective immunogens and antibodies for passive immunization.

PubMed: 33594061
DOI: 10.1038/s41467-021-21221-4

実験手法

X-RAY DIFFRACTION (2.534 Å)