6UUD

Crystal structure of antibody 5D5 in complex with PfCSP N-terminal peptide

6UUD の概要

• エントリーDOI: 10.2210/pdb6uud/pdb
• 分子名称: 5D5 Antibody Fab, heavy chain, 5D5 Antibody Fab, light chain, Circumsporozoite protein, ... (6 entities in total)
• 機能のキーワード: malaria, antibody, immune system
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 49927.73

構造登録者

Thai, E.,Scally, S.W.,Julien, J.P. (登録日: 2019-10-30, 公開日: 2020-07-15, 最終更新日: 2024-11-13)

主引用文献

Thai, E.,Costa, G.,Weyrich, A.,Murugan, R.,Oyen, D.,Flores-Garcia, Y.,Prieto, K.,Bosch, A.,Valleriani, A.,Wu, N.C.,Pholcharee, T.,Scally, S.W.,Wilson, I.A.,Wardemann, H.,Julien, J.P.,Levashina, E.A.
A high-affinity antibody against the CSP N-terminal domain lacks Plasmodium falciparum inhibitory activity.
J.Exp.Med., 217:-, 2020

PubMed Abstract: Malaria is a global health concern, and research efforts are ongoing to develop a superior vaccine to RTS,S/AS01. To guide immunogen design, we seek a comprehensive understanding of the protective humoral response against Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP). In contrast to the well-studied responses to the repeat region and the C-terminus, the antibody response against the N-terminal domain of PfCSP (N-CSP) remains obscure. Here, we characterized the molecular recognition and functional efficacy of the N-CSP-specific monoclonal antibody 5D5. The crystal structure at 1.85-Å resolution revealed that 5D5 binds an α-helical epitope in N-CSP with high affinity through extensive shape and charge complementarity and the unusual utilization of an antibody N-linked glycan. Nevertheless, functional studies indicated low 5D5 binding to live Pf sporozoites and lack of sporozoite inhibition in vitro and in vivo. Overall, our data do not support the inclusion of the 5D5 N-CSP epitope into the next generation of CSP-based vaccines.

PubMed: 32790871
DOI: 10.1084/jem.20200061

実験手法

X-RAY DIFFRACTION (1.85 Å)