7L56

Cryo-EM structure of the SARS-CoV-2 spike glycoprotein bound to Fab 2-43

Summary for 7L56

• Entry DOI: 10.2210/pdb7l56/pdb
• EMDB information: 23165
• Descriptor: Spike glycoprotein, Fab 2-43 variable domain heavy chain, Fab 2-43 variable domain light chain, ... (8 entities in total)
• Functional Keywords: sars-cov-2, spike, glycoprotein, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 9
• Total formula weight: 518147.53

Authors

Rapp, M.,Shapiro, L. (deposition date: 2020-12-21, release date: 2021-04-14, Last modification date: 2023-04-05)

Primary citation

Rapp, M.,Guo, Y.,Reddem, E.R.,Yu, J.,Liu, L.,Wang, P.,Cerutti, G.,Katsamba, P.,Bimela, J.S.,Bahna, F.A.,Mannepalli, S.M.,Zhang, B.,Kwong, P.D.,Huang, Y.,Ho, D.D.,Shapiro, L.,Sheng, Z.
Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class.
Cell Rep, 35:108950-108950, 2021

PubMed Abstract: Antibodies with heavy chains that derive from the VH1-2 gene constitute some of the most potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies yet identified. To provide insight into whether these genetic similarities inform common modes of recognition, we determine the structures of the SARS-CoV-2 spike in complex with three VH1-2-derived antibodies: 2-15, 2-43, and H4. All three use VH1-2-encoded motifs to recognize the receptor-binding domain (RBD), with heavy-chain N53I-enhancing binding and light-chain tyrosines recognizing F486. Despite these similarities, class members bind both RBD-up and -down conformations of the spike, with a subset of antibodies using elongated CDRH3s to recognize glycan N343 on a neighboring RBD-a quaternary interaction accommodated by an increase in RBD separation of up to 12 Å. The VH1-2 antibody class, thus, uses modular recognition encoded by modular genetic elements to effect potent neutralization, with the VH-gene component specifying recognition of RBD and the CDRH3 component specifying quaternary interactions.

PubMed: 33794145
DOI: 10.1016/j.celrep.2021.108950

Experimental method

ELECTRON MICROSCOPY (3.6 Å)