9XAW

Structure of the SARS-CoV-2 Spike N-terminal domain(NTD) in complex with the BLN8 Fab

This is a non-PDB format compatible entry.

Summary for 9XAW

• Entry DOI: 10.2210/pdb9xaw/pdb
• Descriptor: BLN8 heavy chain, Spike protein S1, BLN8 light chain, ... (9 entities in total)
• Functional Keywords: complex, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 12
• Total formula weight: 331993.79

Authors

Zhou, J.J.,Gao, G.F. (deposition date: 2025-10-23, 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

X-RAY DIFFRACTION (3.13 Å)