7PS7

Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-40 Fab

Summary for 7PS7

• Entry DOI: 10.2210/pdb7ps7/pdb
• Related: 7PRY 7PRZ 7PS0 7PS1 7PS2 7PS3 7PS4 7PS5 7PS6
• Descriptor: Spike protein S1, Beta-40 Fab light chain, Beta-40 heavy chain (3 entities in total)
• Functional Keywords: sars-cov-2 b.1.1.7 (alpha) variant, b.1.351 (beta) variant, p.1 (gamma) variant, b.1.617.2 (delta) variant, antibody, receptor-binding-domain, spike, neutralisation, viral protein/immune system, viral protein, immune system, viral protein-immune system complex
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 6
• Total formula weight: 140580.71

Authors

Zhou, D.,Ren, J.,Stuart, D.I. (deposition date: 2021-09-22, release date: 2021-12-15, Last modification date: 2024-10-23)

Primary citation

Liu, C.,Zhou, D.,Nutalai, R.,Duyvesteyn, H.M.E.,Tuekprakhon, A.,Ginn, H.M.,Dejnirattisai, W.,Supasa, P.,Mentzer, A.J.,Wang, B.,Case, J.B.,Zhao, Y.,Skelly, D.T.,Chen, R.E.,Johnson, S.A.,Ritter, T.G.,Mason, C.,Malik, T.,Temperton, N.,Paterson, N.G.,Williams, M.A.,Hall, D.R.,Clare, D.K.,Howe, A.,Goulder, P.J.R.,Fry, E.E.,Diamond, M.S.,Mongkolsapaya, J.,Ren, J.,Stuart, D.I.,Screaton, G.R.
The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants.
Cell Host Microbe, 30:53-, 2022

PubMed Abstract: Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.

PubMed: 34921776
DOI: 10.1016/j.chom.2021.11.013

Experimental method

X-RAY DIFFRACTION (3.9 Å)