8F9S

Crystal structure of Ky15.2 Fab in complex with circumsporozoite protein NDN peptide

8F9S の概要

• エントリーDOI: 10.2210/pdb8f9s/pdb
• 分子名称: Ky15.2 Antibody, heavy chain, Ky15.2 Antibody, light chain, Circumsporozoite protein NDN peptide, ... (5 entities in total)
• 機能のキーワード: malaria, antibody, immune system
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 98225.60

構造登録者

Thai, E.,Julien, J.P. (登録日: 2022-11-24, 公開日: 2023-11-01, 最終更新日: 2024-11-13)

主引用文献

Thai, E.,Murugan, R.,Binter, S.,Burn Aschner, C.,Prieto, K.,Kassardjian, A.,Obraztsova, A.S.,Kang, R.W.,Flores-Garcia, Y.,Mathis-Torres, S.,Li, K.,Horn, G.Q.,Huntwork, R.H.C.,Bolscher, J.M.,de Bruijni, M.H.C.,Sauerwein, R.,Dennison, S.M.,Tomaras, G.D.,Zavala, F.,Kellam, P.,Wardemann, H.,Julien, J.P.
Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparum circumsporozoite protein.
Cell Rep, 42:113330-113330, 2023

PubMed Abstract: IGHV3-33-encoded antibodies are prevalent in the human humoral response against the Plasmodium falciparum circumsporozoite protein (PfCSP). Among VH3-33 antibodies, cross-reactivity between PfCSP major repeat (NANP), minor (NVDP), and junctional (NPDP) motifs is associated with high affinity and potent parasite inhibition. However, the molecular basis of antibody cross-reactivity and the relationship with efficacy remain unresolved. Here, we perform an extensive structure-function characterization of 12 VH3-33 anti-PfCSP monoclonal antibodies (mAbs) with varying degrees of cross-reactivity induced by immunization of mice expressing a human immunoglobulin gene repertoire. We identify residues in the antibody paratope that mediate cross-reactive binding and delineate four distinct epitope conformations induced by antibody binding, with one consistently associated with high protective efficacy and another that confers comparably potent inhibition of parasite liver invasion. Our data show a link between molecular features of cross-reactive VH3-33 mAb binding to PfCSP and mAb potency, relevant for the development of antibody-based interventions against malaria.

PubMed: 38007690
DOI: 10.1016/j.celrep.2023.113330

実験手法

X-RAY DIFFRACTION (2.1 Å)