8DF5

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

8DF5 の概要

• エントリーDOI: 10.2210/pdb8df5/pdb
• 分子名称: S309 Fab Heavy Chain, ZINC ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total)
• 機能のキーワード: rbd, sars-cov-2, covid, s309, beta, b.1.351, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein, viral protein-hydrolase-immune system complex, viral protein/hydrolase/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 440018.04

構造登録者

McCallum, M.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Snell, G.,Veesler, D. (登録日: 2022-06-21, 公開日: 2022-08-03, 最終更新日: 2024-10-23)

主引用文献

Starr, T.N.,Greaney, A.J.,Hannon, W.W.,Loes, A.N.,Hauser, K.,Dillen, J.R.,Ferri, E.,Farrell, A.G.,Dadonaite, B.,McCallum, M.,Matreyek, K.A.,Corti, D.,Veesler, D.,Snell, G.,Bloom, J.D.
Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution.
Science, 377:420-424, 2022

PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites-a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single-amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change-for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.

PubMed: 35762884
DOI: 10.1126/science.abo7896

実験手法

X-RAY DIFFRACTION (2.7 Å)