22GI

3D1 Fab in complex with pepAVVNQN

Summary for 22GI

• Entry DOI: 10.2210/pdb22gi/pdb
• Descriptor: Light chain of 3D1, Heavy chain of 3D1, ALA-VAL-VAL-ASN-GLN-ASN, ... (5 entities in total)
• Functional Keywords: sads-cov, antibody, spike, hr1, viral protein/immune system, viral protein-immune system complex
• Biological source: Homo sapiens; More
• Total number of polymer chains: 12
• Total formula weight: 184204.31

Authors

Lei, Y. (deposition date: 2026-01-09, release date: 2026-04-15)

Primary citation

Zhang, L.,Liang, Z.,Yang, G.,Yan, L.
Elucidating the Molecular Mechanism of 3D1 Antibody Binding to a Swine Enteric Coronavirus Antigen.
Viruses, 18:-, 2026

PubMed Abstract: The broadly neutralizing monoclonal antibody 3D1 potently neutralizes SADS-CoV by targeting a conserved epitope within the heptad repeat 1 (HR1) domain of the viral spike protein. Structural and biophysical analyses demonstrate that 3D1 binds with high affinity to a specific linear β-turn motif (residues A804-N809) in HR1. High-resolution crystallography reveals that this motif sits within a deep, electrostatically complementary paratope groove. Critically, 3D1 binding competitively inhibits the essential interaction between HR1 and HR2. Notably, its recognition is not dependent on HR1's native helical conformation, as it maintains strong binding to conformationally constrained, stapled helical peptides. Collectively, the data indicate that 3D1 neutralizes by capturing a pre-hairpin intermediate state of HR1-a transition state between prefusion and postfusion forms-thereby sterically blocking the formation of the stable postfusion six-helix bundle that is essential for membrane fusion. This work defines a precise, structure-dependent neutralizing epitope and elucidates a mechanism of action that involves trapping a key fusion intermediate, offering a valuable template for the design of broad-spectrum coronavirus therapeutics.

PubMed: 41754551
DOI: 10.3390/v18020208

Experimental method

X-RAY DIFFRACTION (2.64 Å)