7SWW

SARS-CoV-2 Spike NTD in complex with neutralizing Fab SARS2-57 (local refinement)

7SWW の概要

• エントリーDOI: 10.2210/pdb7sww/pdb
• EMDBエントリー: 25487 25488
• 分子名称: Spike protein S1, SARS2-57 Fv heavy chain, SARS2-57 Fv light chain, ... (5 entities in total)
• 機能のキーワード: glycoprotein, antibody, structural genomics, center for structural genomics of infectious diseases, csgid, viral protein-immune system complex, center for structural biology of infectious diseases, csbid, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 60155.07

構造登録者

Adams, L.J.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID),Center for Structural Biology of Infectious Diseases (CSBID) (登録日: 2021-11-21, 公開日: 2022-11-23, 最終更新日: 2025-09-24)

主引用文献

Adams, L.J.,VanBlargan, L.A.,Liu, Z.,Gilchuk, P.,Zhao, H.,Chen, R.E.,Raju, S.,Chong, Z.,Whitener, B.M.,Shrihari, S.,Jethva, P.N.,Gross, M.L.,Crowe Jr., J.E.,Whelan, S.P.J.,Diamond, M.S.,Fremont, D.H.
A broadly reactive antibody targeting the N-terminal domain of SARS-CoV-2 spike confers Fc-mediated protection.
Cell Rep Med, 4:101305-101305, 2023

PubMed Abstract: Most neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) target the receptor binding domain (RBD) of the spike (S) protein. Here, we characterize a panel of mAbs targeting the N-terminal domain (NTD) or other non-RBD epitopes of S. A subset of NTD mAbs inhibits SARS-CoV-2 entry at a post-attachment step and avidly binds the surface of infected cells. One neutralizing NTD mAb, SARS2-57, protects K18-hACE2 mice against SARS-CoV-2 infection in an Fc-dependent manner. Structural analysis demonstrates that SARS2-57 engages an antigenic supersite that is remodeled by deletions common to emerging variants. In neutralization escape studies with SARS2-57, this NTD site accumulates mutations, including a similar deletion, but the addition of an anti-RBD mAb prevents such escape. Thus, our study highlights a common strategy of immune evasion by SARS-CoV-2 variants and how targeting spatially distinct epitopes, including those in the NTD, may limit such escape.

PubMed: 38039973
DOI: 10.1016/j.xcrm.2023.101305

実験手法

ELECTRON MICROSCOPY (3.13 Å)