8CWV

Crystal structure of SARS-CoV-2 spike protein receptor-binding domain in complex with a cross-neutralizing nanobody 2-31 and a human antibody CC12.1 Fab

8CWV の概要

• エントリーDOI: 10.2210/pdb8cwv/pdb
• 分子名称: Spike protein S1, VHH 2-31, CC12.1 Fab heavy chain, ... (5 entities in total)
• 機能のキーワード: cross-neutralizing antibody; nanobody; sars-cov-2; sarbecovirus; immune system; vhh; cc12.1, immune system
• 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: 4
• 化学式量合計: 87716.71

構造登録者

Liu, H.,Wilson, I.A. (登録日: 2022-05-19, 公開日: 2022-07-06, 最終更新日: 2024-10-23)

主引用文献

Xiang, Y.,Huang, W.,Liu, H.,Sang, Z.,Nambulli, S.,Tubiana, J.,Williams Jr., K.L.,Duprex, W.P.,Schneidman-Duhovny, D.,Wilson, I.A.,Taylor, D.J.,Shi, Y.
Superimmunity by pan-sarbecovirus nanobodies.
Cell Rep, 39:111004-111004, 2022

PubMed Abstract: Vaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observe superimmunity in a camelid extensively immunized with the SARS-CoV-2 receptor-binding domain (RBD). We rapidly isolate a large repertoire of specific ultra-high-affinity nanobodies that bind strongly to all known sarbecovirus clades using integrative proteomics. These pan-sarbecovirus nanobodies (psNbs) are highly effective against SARS-CoV and SARS-CoV-2 variants, including Omicron, with the best median neutralization potency at single-digit nanograms per milliliter. A highly potent, inhalable, and bispecific psNb (PiN-31) is also developed. Structural determinations of 13 psNbs with the SARS-CoV-2 spike or RBD reveal five epitope classes, providing insights into the mechanisms and evolution of their broad activities. The highly evolved psNbs target small, flat, and flexible epitopes that contain over 75% of conserved RBD surface residues. Their potencies are strongly and negatively correlated with the distance of the epitopes from the receptor binding sites.

PubMed: 35738279
DOI: 10.1016/j.celrep.2022.111004

実験手法

X-RAY DIFFRACTION (2.51 Å)