7KN4

Crystal structure of SARS-CoV-2 spike protein receptor-binding domain complexed with a pre-pandemic antibody S-E6 Fab

Summary for 7KN4

• Entry DOI: 10.2210/pdb7kn4/pdb
• Descriptor: Spike protein S1, S-E6 Fab heavy chain, S-E6 Fab light chain, ... (4 entities in total)
• Functional Keywords: sars-cov-2, antibody, spike, coronavirus, covid-19, immune system, viral protein-immune system complex, phage display, pre-pandemic, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 6
• Total formula weight: 145474.69

Authors

Liu, H.,Wilson, I.A. (deposition date: 2020-11-04, release date: 2021-09-22, Last modification date: 2024-11-06)

Primary citation

Qiang, M.,Ma, P.,Li, Y.,Liu, H.,Harding, A.,Min, C.,Wang, F.,Liu, L.,Yuan, M.,Ji, Q.,Tao, P.,Shi, X.,Li, Z.,Li, T.,Wang, X.,Zhang, Y.,Wu, N.C.,Lee, C.D.,Zhu, X.,Gilbert-Jaramillo, J.,Zhang, C.,Saxena, A.,Huang, X.,Wang, H.,James, W.,Dwek, R.A.,Wilson, I.A.,Yang, G.,Lerner, R.A.
Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades Ago.
Adv Sci, 9:e2102181-e2102181, 2022

PubMed Abstract: Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, a combinatorial human antibody library constructed 20 years before the coronavirus disease 2019 (COVID-19) pandemic is used to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these three antibodies contain over 13-22 SHMs, many of which are involved in specific interactions in their crystal structures with SARS-CoV-2 spike receptor binding domain. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of these antibodies with respect to their reactivity with SARS-CoV-2.

PubMed: 34716683
DOI: 10.1002/advs.202102181

Experimental method

X-RAY DIFFRACTION (2.7 Å)