7SN0

Crystal structure of spike protein receptor binding domain of escape mutant SARS-CoV-2 from immunocompromised patient (d146*) in complex with human receptor ACE2

7SN0 の概要

• エントリーDOI: 10.2210/pdb7sn0/pdb
• 分子名称: Angiotensin-converting enzyme 2, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)]alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (13 entities in total)
• 機能のキーワード: covid-19, sars-cov-2, spike protein, neutralization escape mutant, ace2, receptor binding, viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 217113.63

構造登録者

Pan, J.,Abraham, J.,Clark, S. (登録日: 2021-10-27, 公開日: 2021-12-08, 最終更新日: 2024-11-06)

主引用文献

Nabel, K.G.,Clark, S.A.,Shankar, S.,Pan, J.,Clark, L.E.,Yang, P.,Coscia, A.,McKay, L.G.A.,Varnum, H.H.,Brusic, V.,Tolan, N.V.,Zhou, G.,Desjardins, M.,Turbett, S.E.,Kanjilal, S.,Sherman, A.C.,Dighe, A.,LaRocque, R.C.,Ryan, E.T.,Tylek, C.,Cohen-Solal, J.F.,Darcy, A.T.,Tavella, D.,Clabbers, A.,Fan, Y.,Griffiths, A.,Correia, I.R.,Seagal, J.,Baden, L.R.,Charles, R.C.,Abraham, J.
Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain.
Science, 375:eabl6251-eabl6251, 2022

PubMed Abstract: Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.

PubMed: 34855508
DOI: 10.1126/science.abl6251

実験手法

X-RAY DIFFRACTION (3.08 Å)