9WIG

Structure of the PT NTD-C1536-CoV2-3434-BLN8 complex

Summary for 9WIG

• Entry DOI: 10.2210/pdb9wig/pdb
• EMDB information: 65993
• Descriptor: 3434-A-2, 3434-B-1, C1536-A-1, ... (8 entities in total)
• Functional Keywords: fab, protein binding/viral protein, viral protein-protein binding complex, viral protein/protein binding
• Biological source: Homo sapiens; More
• Total number of polymer chains: 7
• Total formula weight: 174140.91

Authors

Sun, J.Q.,Zhou, J.J. (deposition date: 2025-08-27, release date: 2026-08-05, Last modification date: 2026-09-16)

Primary citation

Zhou, J.,Li, W.,Wang, X.,Sun, J.,Guo, S.,Rong, X.,Tong, Z.,Dai, L.,Liu, W.J.,Qi, J.,Gao, G.F.,Wang, Q.
A structural and mechanistic atlas of NTD antibody neutralization and immune escape across SARS-CoV-2 prototype and its (sub-)variants.
Proc.Natl.Acad.Sci.USA, 123:e2535385123-e2535385123, 2026

PubMed Abstract: The N-terminal domain (NTD) of the SARS-CoV-2 spike (S) is a critical antibody target, yet its epitope organization, neutralization mechanisms, and immune evasion strategies remain incompletely resolved. Here, we classify NTD antibodies into nine spatially distinct classes (designated as NTD-1 to NTD-9), including a cryptic epitope defined here (NTD-8). Mechanistic studies reveal that NTD-5 and NTD-9 antibodies neutralize by inducing S1 shedding, thereby extending this mechanism to selected NTD-directed antibodies. Format profiling shows that while most NTD antibodies require bivalency, selected antibodies from NTD-3, NTD-5, and NTD-9 retain neutralizing activity in Fab form. Profiling 41 antibodies across prototype, Delta, and 17 Omicron subvariants defines an epitope-resolved escape landscape and enables dissection of three convergent evasion strategies: contact residue disruption, glycan shielding, and conformational remodeling. Notably, the KP.3.1.1 subvariant uses a dual escape mechanism in which ∆S31 introduces N30 glycosylation and substantially remodels the S27-R34 region, undermining recognition by both NTD-5 and NTD-9 antibodies. These findings provide a structural and mechanistic framework for rational vaccine and antibody design resilient to antigenic drift.

PubMed: 42555640
DOI: 10.1073/pnas.2535385123

Experimental method

ELECTRON MICROSCOPY (3.93 Å)