7NX8

Crystal structure of the K417T mutant receptor binding domain of SARS-CoV-2 Spike glycoprotein in complex with COVOX-222 and EY6A Fabs

7NX8 の概要

• エントリーDOI: 10.2210/pdb7nx8/pdb
• 関連するPDBエントリー: 7NX6 7NX7
• 分子名称: EY6A Fab heavy chain, CITRIC ACID, CHLORIDE ION, ... (12 entities in total)
• 機能のキーワード: sars-cov-2 b.1.1.7 variant, b.1.351 variant, p.1 variant, antibody, receptor-binding-domain, spike, neutralisation, viral protein/immune system, viral protein, immune system, viral protein-immune system complex
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 120089.00

構造登録者

Zhou, D.,Ren, J.,Stuart, D. (登録日: 2021-03-17, 公開日: 2021-04-07, 最終更新日: 2024-10-09)

主引用文献

Dejnirattisai, W.,Zhou, D.,Supasa, P.,Liu, C.,Mentzer, A.J.,Ginn, H.M.,Zhao, Y.,Duyvesteyn, H.M.E.,Tuekprakhon, A.,Nutalai, R.,Wang, B.,Lopez-Camacho, C.,Slon-Campos, J.,Walter, T.S.,Skelly, D.,Costa Clemens, S.A.,Naveca, F.G.,Nascimento, V.,Nascimento, F.,Fernandes da Costa, C.,Resende, P.C.,Pauvolid-Correa, A.,Siqueira, M.M.,Dold, C.,Levin, R.,Dong, T.,Pollard, A.J.,Knight, J.C.,Crook, D.,Lambe, T.,Clutterbuck, E.,Bibi, S.,Flaxman, A.,Bittaye, M.,Belij-Rammerstorfer, S.,Gilbert, S.C.,Carroll, M.W.,Klenerman, P.,Barnes, E.,Dunachie, S.J.,Paterson, N.G.,Williams, M.A.,Hall, D.R.,Hulswit, R.J.G.,Bowden, T.A.,Fry, E.E.,Mongkolsapaya, J.,Ren, J.,Stuart, D.I.,Screaton, G.R.
Antibody evasion by the P.1 strain of SARS-CoV-2.
Cell, 184:2939-, 2021

PubMed Abstract: Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

PubMed: 33852911
DOI: 10.1016/j.cell.2021.03.055

実験手法

X-RAY DIFFRACTION (1.95 Å)