7UZC

Structure of the SARS-CoV-2 RBD in complex with the mouse antibody Fab fragment, M8a-34

7UZC の概要

• エントリーDOI: 10.2210/pdb7uzc/pdb
• 分子名称: Spike protein S1, M8a-34 Fab heavy chain, M8a-34 Fab light chain, ... (6 entities in total)
• 機能のキーワード: immune system, neutralizing antibody, immune system-viral protein complex, immune system/viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 152574.29

構造登録者

Fan, C.,Bjorkman, P.J. (登録日: 2022-05-08, 公開日: 2023-01-11, 最終更新日: 2024-10-16)

主引用文献

Fan, C.,Cohen, A.A.,Park, M.,Hung, A.F.,Keeffe, J.R.,Gnanapragasam, P.N.P.,Lee, Y.E.,Gao, H.,Kakutani, L.M.,Wu, Z.,Kleanthous, H.,Malecek, K.E.,Williams, J.C.,Bjorkman, P.J.
Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes.
Immunity, 55:2419-2435.e10, 2022

PubMed Abstract: Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer cross-linking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb-resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs.

PubMed: 36370711
DOI: 10.1016/j.immuni.2022.10.019

実験手法

X-RAY DIFFRACTION (2.2 Å)