7E5O

Crystal structure of SARS-CoV-2 RBD in complex with antibody NT-193

7E5O の概要

• エントリーDOI: 10.2210/pdb7e5o/pdb
• 分子名称: NT-193 Heavy chain, NT-193 Light chain, Spike protein S1, ... (5 entities in total)
• 機能のキーワード: spike, igg, viral protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 74064.90

構造登録者

Kita, S.,Onodera, T.,Adachi, Y.,Moriayma, S.,Nomura, T.,Tadokoro, T.,Anraku, Y.,Yumoto, K.,Tian, C.,Fukuhara, H.,Suzuki, T.,Tonouchi, K.,Sasaki, J.,Sun, L.,Hashiguchi, T.,Takahashi, Y.,Maenaka, K. (登録日: 2021-02-19, 公開日: 2021-09-08, 最終更新日: 2024-10-23)

主引用文献

Onodera, T.,Kita, S.,Adachi, Y.,Moriyama, S.,Sato, A.,Nomura, T.,Sakakibara, S.,Inoue, T.,Tadokoro, T.,Anraku, Y.,Yumoto, K.,Tian, C.,Fukuhara, H.,Sasaki, M.,Orba, Y.,Shiwa, N.,Iwata, N.,Nagata, N.,Suzuki, T.,Sasaki, J.,Sekizuka, T.,Tonouchi, K.,Sun, L.,Fukushi, S.,Satofuka, H.,Kazuki, Y.,Oshimura, M.,Kurosaki, T.,Kuroda, M.,Matsuura, Y.,Suzuki, T.,Sawa, H.,Hashiguchi, T.,Maenaka, K.,Takahashi, Y.
A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site.
Immunity, 54:2385-, 2021

PubMed Abstract: Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but the variability of RBS epitopes hampers broad neutralization of multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an RBS antibody with a germline V gene that potently neutralized SARS-related coronaviruses, including SARS-CoV and SARS-CoV-2 variants. X-ray crystallography revealed coordinated recognition by the heavy chain of non-RBS conserved sites and the light chain of RBS with a binding angle mimicking the angiotensin-converting enzyme 2 (ACE2) receptor. The minimum footprints in the hypervariable region of RBS contributed to the breadth of neutralization, which was enhanced by immunoglobulin G3 (IgG3) class switching. The coordinated binding resulted in broad neutralization of SARS-CoV and emerging SARS-CoV-2 variants of concern. Low-dose therapeutic antibody treatment in hamsters reduced the virus titers and morbidity during SARS-CoV-2 challenge. The structural basis for broad neutralizing activity may inform the design of a broad spectrum of therapeutics and vaccines.

PubMed: 34508662
DOI: 10.1016/j.immuni.2021.08.025

実験手法

X-RAY DIFFRACTION (2.8 Å)