7KS9

Cryo-EM structure of prefusion SARS-CoV-2 spike glycoprotein in complex with 910-30 Fab

Summary for 7KS9

• Entry DOI: 10.2210/pdb7ks9/pdb
• EMDB information: 23016
• Descriptor: 910-30 Fab light chain, 910-30 Fab heavy chain, Spike glycoprotein, ... (5 entities in total)
• Functional Keywords: neutralizing antibody, fusion protein, spike glycoprotein, covid-19, rbd, viral protein, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 5
• Total formula weight: 486963.44

Authors

Cerutti, G.,Shapiro, L. (deposition date: 2020-11-21, release date: 2021-02-10, Last modification date: 2024-11-13)

Primary citation

Banach, B.B.,Cerutti, G.,Fahad, A.S.,Shen, C.H.,Oliveira De Souza, M.,Katsamba, P.S.,Tsybovsky, Y.,Wang, P.,Nair, M.S.,Huang, Y.,Francino-Urdaniz, I.M.,Steiner, P.J.,Gutierrez-Gonzalez, M.,Liu, L.,Lopez Acevedo, S.N.,Nazzari, A.F.,Wolfe, J.R.,Luo, Y.,Olia, A.S.,Teng, I.T.,Yu, J.,Zhou, T.,Reddem, E.R.,Bimela, J.,Pan, X.,Madan, B.,Laflin, A.D.,Nimrania, R.,Yuen, K.Y.,Whitehead, T.A.,Ho, D.D.,Kwong, P.D.,Shapiro, L.,DeKosky, B.J.
Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses.
Cell Rep, 37:109771-109771, 2021

PubMed Abstract: Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be ∼1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.

PubMed: 34587480
DOI: 10.1016/j.celrep.2021.109771

Experimental method

ELECTRON MICROSCOPY (4.75 Å)