7MSQ

Complex between the Fab arm of AB-3467 and the SARS-CoV-2 receptor binding domain (RBD)

Summary for 7MSQ

• Entry DOI: 10.2210/pdb7msq/pdb
• Descriptor: Spike protein S1, AB-3467 Fab Heavy Chain, AB-3467 Fab Light Chain, ... (8 entities in total)
• Functional Keywords: sars-cov-2 receptor binding domain ab-3467, antiviral protein, viral protein-antiviral protein complex, viral protein/antiviral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 6
• Total formula weight: 145714.09

Authors

Langley, D.B.,Christ, D. (deposition date: 2021-05-12, release date: 2022-01-19, Last modification date: 2024-10-23)

Primary citation

Burnett, D.L.,Jackson, K.J.L.,Langley, D.B.,Aggrawal, A.,Stella, A.O.,Johansen, M.D.,Balachandran, H.,Lenthall, H.,Rouet, R.,Walker, G.,Saunders, B.M.,Singh, M.,Li, H.,Henry, J.Y.,Jackson, J.,Stewart, A.G.,Witthauer, F.,Spence, M.A.,Hansbro, N.G.,Jackson, C.,Schofield, P.,Milthorpe, C.,Martinello, M.,Schulz, S.R.,Roth, E.,Kelleher, A.,Emery, S.,Britton, W.J.,Rawlinson, W.D.,Karl, R.,Schafer, S.,Winkler, T.H.,Brink, R.,Bull, R.A.,Hansbro, P.M.,Jack, H.M.,Turville, S.,Christ, D.,Goodnow, C.C.
Immunizations with diverse sarbecovirus receptor-binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability.
Immunity, 54:2908-2921.e6, 2021

PubMed Abstract: Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that are evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse sarbecovirus receptor-binding domains (RBDs) to identify antibodies targeting conserved sites of vulnerability. Antibodies with broad reactivity against diverse clade B RBDs targeting the conserved class 4 epitope, with recurring IGHV/IGKV pairs, were readily elicited but were non-neutralizing. However, rare class 4 antibodies binding this conserved RBD supersite showed potent neutralization of SARS-CoV-2 and all variants of concern. Structural analysis revealed that the neutralizing ability of cross-reactive antibodies was reserved only for those with an elongated CDRH3 that extends the antiparallel beta-sheet RBD core and orients the antibody light chain to obstruct ACE2-RBD interactions. These results identify a structurally defined pathway for vaccine strategies eliciting escape-resistant SARS-CoV-2 neutralizing antibodies.

PubMed: 34788600
DOI: 10.1016/j.immuni.2021.10.019

Experimental method

X-RAY DIFFRACTION (2.29 Å)