7RKS

Structure of the SARS-CoV receptor binding domain in complex with the human neutralizing antibody Fab fragment, C118

Summary for 7RKS

• Entry DOI: 10.2210/pdb7rks/pdb
• Descriptor: C118 Antibody Fab Heavy Chain, C118 Antibody Fab Light Chain, Spike protein S1, ... (5 entities in total)
• Functional Keywords: antibody, surface protein, fab, coronavirus, fusion protein, binding domain, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 142586.78

Authors

Jette, C.A.,Bjorkman, P.J.,Barnes, C.O. (deposition date: 2021-07-22, release date: 2021-09-22, Last modification date: 2024-11-06)

Primary citation

Jette, C.A.,Cohen, A.A.,Gnanapragasam, P.N.P.,Muecksch, F.,Lee, Y.E.,Huey-Tubman, K.E.,Schmidt, F.,Hatziioannou, T.,Bieniasz, P.D.,Nussenzweig, M.C.,West Jr., A.P.,Keeffe, J.R.,Bjorkman, P.J.,Barnes, C.O.
Broad cross-reactivity across sarbecoviruses exhibited by a subset of COVID-19 donor-derived neutralizing antibodies.
Cell Rep, 36:109760-109760, 2021

PubMed Abstract: Many anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) neutralizing antibodies target the angiotensin-converting enzyme 2 (ACE2) binding site on viral spike receptor-binding domains (RBDs). Potent antibodies recognize exposed variable epitopes, often rendering them ineffective against other sarbecoviruses and SARS-CoV-2 variants. Class 4 anti-RBD antibodies against a less-exposed, but more-conserved, cryptic epitope could recognize newly emergent zoonotic sarbecoviruses and variants, but they usually show only weak neutralization potencies. Here, we characterize two class 4 anti-RBD antibodies derived from coronavirus disease 2019 (COVID-19) donors that exhibit breadth and potent neutralization of zoonotic coronaviruses and SARS-CoV-2 variants. C118-RBD and C022-RBD structures reveal orientations that extend from the cryptic epitope to occlude ACE2 binding and CDRH3-RBD main-chain H-bond interactions that extend an RBD β sheet, thus reducing sensitivity to RBD side-chain changes. A C118-spike trimer structure reveals rotated RBDs that allow access to the cryptic epitope and the potential for intra-spike crosslinking to increase avidity. These studies facilitate vaccine design and illustrate potential advantages of class 4 RBD-binding antibody therapeutics.

PubMed: 34534459
DOI: 10.1016/j.celrep.2021.109760

Experimental method

X-RAY DIFFRACTION (2.7 Å)