8A99

SARS Cov2 Spike in 1-up conformation complex with Fab47

Summary for 8A99

• Entry DOI: 10.2210/pdb8a99/pdb
• EMDB information: 15273
• Descriptor: SARS-CoV2 spike 1-up conformation in complex with Fab47, Fab47 (Heavy chain variable domain), Fab47 (Light chain Variable domain), ... (5 entities in total)
• Functional Keywords: spike, antibody, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 9
• Total formula weight: 515070.42

Authors

Hallberg, B.M.,Das, H. (deposition date: 2022-06-28, release date: 2023-05-10, Last modification date: 2024-10-16)

Primary citation

Pushparaj, P.,Nicoletto, A.,Sheward, D.J.,Das, H.,Castro Dopico, X.,Perez Vidakovics, L.,Hanke, L.,Chernyshev, M.,Narang, S.,Kim, S.,Fischbach, J.,Ekstrom, S.,McInerney, G.,Hallberg, B.M.,Murrell, B.,Corcoran, M.,Karlsson Hedestam, G.B.
Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodies.
Immunity, 56:193-206.e7, 2023

PubMed Abstract: The human immunoglobulin heavy-chain (IGH) locus is exceptionally polymorphic, with high levels of allelic and structural variation. Thus, germline IGH genotypes are personal, which may influence responses to infection and vaccination. For an improved understanding of inter-individual differences in antibody responses, we isolated SARS-CoV-2 spike-specific monoclonal antibodies from convalescent health care workers, focusing on the IGHV1-69 gene, which has the highest level of allelic variation of all IGHV genes. The IGHV1-6920-using CAB-I47 antibody and two similar antibodies isolated from an independent donor were critically dependent on allele usage. Neutralization was retained when reverting the V region to the germline IGHV1-6920 allele but lost when reverting to other IGHV1-69 alleles. Structural data confirmed that two germline-encoded polymorphisms, R50 and F55, in the IGHV1-69 gene were required for high-affinity receptor-binding domain interaction. These results demonstrate that polymorphisms in IGH genes can influence the function of SARS-CoV-2 neutralizing antibodies.

PubMed: 36574772
DOI: 10.1016/j.immuni.2022.12.005

Experimental method

ELECTRON MICROSCOPY (2.5 Å)