7LY3

Crystal structure of SARS-CoV-2 S NTD bound to S2M28 Fab

Summary for 7LY3

• Entry DOI: 10.2210/pdb7ly3/pdb
• Descriptor: Spike protein S1, SULFATE ION, S2M28 Fab Heavy Chain, ... (10 entities in total)
• Functional Keywords: antibody, viral protein, structural genomics, seattle structural genomics center for infectious disease, ssgcid, 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: 6
• Total formula weight: 175339.01

Authors

McCallum, M.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2021-03-05, release date: 2021-04-14, Last modification date: 2024-10-30)

Primary citation

McCallum, M.,De Marco, A.,Lempp, F.A.,Tortorici, M.A.,Pinto, D.,Walls, A.C.,Beltramello, M.,Chen, A.,Liu, Z.,Zatta, F.,Zepeda, S.,di Iulio, J.,Bowen, J.E.,Montiel-Ruiz, M.,Zhou, J.,Rosen, L.E.,Bianchi, S.,Guarino, B.,Fregni, C.S.,Abdelnabi, R.,Foo, S.C.,Rothlauf, P.W.,Bloyet, L.M.,Benigni, F.,Cameroni, E.,Neyts, J.,Riva, A.,Snell, G.,Telenti, A.,Whelan, S.P.J.,Virgin, H.W.,Corti, D.,Pizzuto, M.S.,Veesler, D.
N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2.
Cell, 184:2332-, 2021

PubMed Abstract: The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite (designated site i) recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge, albeit selecting escape mutants in some animals. Indeed, several SARS-CoV-2 variants, including the B.1.1.7, B.1.351, and P.1 lineages, harbor frequent mutations within the NTD supersite, suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs for protective immunity and vaccine design.

PubMed: 33761326
DOI: 10.1016/j.cell.2021.03.028

Experimental method

X-RAY DIFFRACTION (3 Å)