7URQ

Crystal Structure of SARS-CoV-2 S delta variant receptor-binding domain (RBD) in complex CoV11 Fab crystal form 1

Summary for 7URQ

• Entry DOI: 10.2210/pdb7urq/pdb
• Related: 7S4S
• Descriptor: Spike protein S1, COV11 Fab HEAVY CHAIN, COV11 Fab LIGHT CHAIN, ... (6 entities in total)
• Functional Keywords: sars-cov-2 s rbd fab complex, sars-cov-2 s receptor-binding domain antibody fab complex, covid-19 spike protein antibody fab complex, delta variant, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 73257.81

Authors

Tolbert, W.D.,Pazgier, M. (deposition date: 2022-04-22, release date: 2022-05-04, Last modification date: 2024-10-16)

Primary citation

Tolbert, W.D.,Chen, Y.,Sun, L.,Benlarbi, M.,Ding, S.,Manickam, R.,Pangaro, E.,Nguyen, D.N.,Gottumukkala, S.,Cote, M.,Gonzalez, F.J.,Finzi, A.,Tehrani, Z.R.,Sajadi, M.M.,Pazgier, M.
The molecular basis of the neutralization breadth of the RBD-specific antibody CoV11.
Front Immunol, 14:1178355-1178355, 2023

PubMed Abstract: SARS-CoV-2, the virus behind the COVID-19 pandemic, has changed over time to the extent that the current virus is substantially different from what originally led to the pandemic in 2019-2020. Viral variants have modified the severity and transmissibility of the disease and continue do so. How much of this change is due to viral fitness versus a response to immune pressure is hard to define. One class of antibodies that continues to afford some level of protection from emerging variants are those that closely overlap the binding site for angiotensin-converting enzyme 2 (ACE2) on the receptor binding domain (RBD). Some members of this class that were identified early in the course of the pandemic arose from the V 3-53 germline gene (IGHV3-53*01) and had short heavy chain complementarity-determining region 3s (CDR H3s). Here, we describe the molecular basis of the SARS-CoV-2 RBD recognition by the anti-RBD monoclonal antibody CoV11 isolated early in the COVID-19 pandemic and show how its unique mode of binding the RBD determines its neutralization breadth. CoV11 utilizes a heavy chain V 3-53 and a light chain V 3-20 germline sequence to bind to the RBD. Two of CoV11's four heavy chain changes from the V 3-53 germline sequence, to Ile and to Arg, and some unique features in its CDR H3 increase its affinity to the RBD, while the four light chain changes from the V 3-20 germline sequence sit outside of the RBD binding site. Antibodies of this type can retain significant affinity and neutralization potency against variants of concern (VOCs) that have diverged significantly from original virus lineage such as the prevalent omicron variant. We also discuss the mechanism by which V 3-53 encoded antibodies recognize spike antigen and show how minimal changes to their sequence, their choice of light chain, and their mode of binding influence their affinity and impact their neutralization breadth.

PubMed: 37334379
DOI: 10.3389/fimmu.2023.1178355

Experimental method

X-RAY DIFFRACTION (2.05 Å)