7RKV

Structure of the SARS-CoV-2 S 6P trimer in complex with neutralizing antibody C118 (State 1)

Summary for 7RKV

• Entry DOI: 10.2210/pdb7rkv/pdb
• Related: 7RKS 7RKU
• EMDB information: 24504
• Descriptor: Spike glycoprotein, C118 Fab Heavy Chain, C118 Fab Light Chain, ... (4 entities in total)
• Functional Keywords: sars-cov-2, broadly neutralizing, coronavirus, antibody, virus, antiviral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 9
• Total formula weight: 578670.95

Authors

Barnes, C.O.,Jette, C.A.,Bjorkman, P.J. (deposition date: 2021-07-22, release date: 2021-09-22, Last modification date: 2025-05-21)

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

ELECTRON MICROSCOPY (3.45 Å)