7U09

Crystal Structure of C13B8 Fab in complex with SARS-CoV-2 S fusion peptide

Summary for 7U09

• Entry DOI: 10.2210/pdb7u09/pdb
• Descriptor: Heavy chain Fab C13B8, Light chain Fab C13B8, SARS-CoV-2 S fusion peptide, ... (4 entities in total)
• Functional Keywords: sars-cov-2 spike, covid-19, fusion peptide, fab, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 49065.80

Authors

Tortorici, M.A.,Veesler, D. (deposition date: 2022-02-17, release date: 2022-08-03, Last modification date: 2023-10-18)

Primary citation

Low, J.S.,Jerak, J.,Tortorici, M.A.,McCallum, M.,Pinto, D.,Cassotta, A.,Foglierini, M.,Mele, F.,Abdelnabi, R.,Weynand, B.,Noack, J.,Montiel-Ruiz, M.,Bianchi, S.,Benigni, F.,Sprugasci, N.,Joshi, A.,Bowen, J.E.,Stewart, C.,Rexhepaj, M.,Walls, A.C.,Jarrossay, D.,Morone, D.,Paparoditis, P.,Garzoni, C.,Ferrari, P.,Ceschi, A.,Neyts, J.,Purcell, L.A.,Snell, G.,Corti, D.,Lanzavecchia, A.,Veesler, D.,Sallusto, F.
ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies.
Science, 377:735-742, 2022

PubMed Abstract: The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus spike proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide and acquire affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha- and betacoronaviruses, including animal coronaviruses WIV-1 and PDF-2180. Two selected mAbs also neutralize Omicron BA.1 and BA.2 authentic viruses and reduce viral burden and pathology in vivo. Structural and functional analyses showed that the fusion peptide-specific mAbs bound with different modalities to a cryptic epitope hidden in prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs.

PubMed: 35857703
DOI: 10.1126/science.abq2679

Experimental method

X-RAY DIFFRACTION (2.1 Å)