7TN0

SARS-CoV-2 Omicron RBD in complex with human ACE2 and S304 Fab and S309 Fab

Summary for 7TN0

• Entry DOI: 10.2210/pdb7tn0/pdb
• Related: 7TLY 7TLZ 7TM0 7TNO
• EMDB information: 25990 25991 25992 25993
• Descriptor: S309 light chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, S309 heavy chain, ... (11 entities in total)
• Functional Keywords: covid-19, sars-cov-2, neutralizing monoclonal antibody, sars-cov-2 receptor human ace2, viral protein-immune system complex, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 12
• Total formula weight: 382458.66

Authors

McCallum, M.,Czudnochowski, N.,Nix, J.C.,Croll, T.I.,SSGCID,Dillen, J.R.,Snell, G.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2022-01-20, release date: 2022-02-02, Last modification date: 2023-10-18)

Primary citation

McCallum, M.,Czudnochowski, N.,Rosen, L.E.,Zepeda, S.K.,Bowen, J.E.,Walls, A.C.,Hauser, K.,Joshi, A.,Stewart, C.,Dillen, J.R.,Powell, A.E.,Croll, T.I.,Nix, J.,Virgin, H.W.,Corti, D.,Snell, G.,Veesler, D.
Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement.
Science, 375:864-868, 2022

PubMed Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation of numerous spike mutations. To understand the Omicron antigenic shift, we determined cryo-electron microscopy and x-ray crystal structures of the spike protein and the receptor-binding domain bound to the broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb of sotrovimab) and to the human ACE2 receptor. We provide a blueprint for understanding the marked reduction of binding of other therapeutic mAbs that leads to dampened neutralizing activity. Remodeling of interactions between the Omicron receptor-binding domain and human ACE2 likely explains the enhanced affinity for the host receptor relative to the ancestral virus.

PubMed: 35076256
DOI: 10.1126/science.abn8652

Experimental method

X-RAY DIFFRACTION (2.85 Å)