7LS9

Cryo-EM structure of neutralizing antibody 1-57 in complex with prefusion SARS-CoV-2 spike glycoprotein

Summary for 7LS9

• Entry DOI: 10.2210/pdb7ls9/pdb
• EMDB information: 23506
• Descriptor: Spike glycoprotein, 1-57 Fab heavy chain, 1-57 Fab light chain, ... (6 entities in total)
• Functional Keywords: neutralizing antibody, fusion protein, spike glycoprotein, covid-19, rbd, rbd-directed antibody, 1-57, viral protein, immune system, 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: 592526.31

Authors

Cerutti, G.,Shapiro, L. (deposition date: 2021-02-17, release date: 2021-03-17, Last modification date: 2024-10-09)

Primary citation

Cerutti, G.,Rapp, M.,Guo, Y.,Bahna, F.,Bimela, J.,Reddem, E.R.,Yu, J.,Wang, P.,Liu, L.,Huang, Y.,Ho, D.D.,Kwong, P.D.,Sheng, Z.,Shapiro, L.
Structural basis for accommodation of emerging B.1.351 and B.1.1.7 variants by two potent SARS-CoV-2 neutralizing antibodies.
Structure, 29:655-663.e4, 2021

PubMed Abstract: Emerging SARS-CoV-2 strains, B.1.1.7 and B.1.351, from the UK and South Africa, respectively, show decreased neutralization by monoclonal antibodies and convalescent or vaccinee sera raised against the original wild-type virus, and are thus of clinical concern. However, the neutralization potency of two antibodies, 1-57 and 2-7, which target the receptor-binding domain (RBD) of the spike, was unaffected by these emerging strains. Here, we report cryo-EM structures of 1-57 and 2-7 in complex with spike, revealing each of these antibodies to utilize a distinct mechanism to bypass or accommodate RBD mutations. Notably, each antibody represented an immune response with recognition distinct from those of frequent antibody classes. Moreover, many epitope residues recognized by 1-57 and 2-7 were outside hotspots of evolutionary pressure for ACE2 binding and neutralizing antibody escape. We suggest the therapeutic use of antibodies, such as 1-57 and 2-7, which target less prevalent epitopes, could ameliorate issues of monoclonal antibody escape.

PubMed: 34111408
DOI: 10.1016/j.str.2021.05.014

Experimental method

ELECTRON MICROSCOPY (3.42 Å)