7Y8J

3D1 in complex with 6-mer HR1 peptide from SARS-CoV-2

Summary for 7Y8J

• Entry DOI: 10.2210/pdb7y8j/pdb
• Descriptor: heavy chain of 3D1, Spike protein S2', light chain of 3D1, ... (4 entities in total)
• Functional Keywords: human antibody, broad, coronavirus, antimicrobial protein, antimicrobial protein-immune system complex, antimicrobial protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 25501.88

Authors

Lei, Y. (deposition date: 2022-06-24, release date: 2023-07-12, Last modification date: 2025-08-27)

Primary citation

Yan, L.,Wang, F.,Hill, M.,Brun, J.,Liang, Z.,Shi, X.,Zhang, L.,He, X.,Li, Y.,Huang, Q.,Dong, X.,Liu, H.,Zhang, Y.,Liu, L.,Dwek, R.A.,Zitzmann, N.,Liang, A.,Yang, G.
A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses.
Nat Commun, 16:7580-7580, 2025

PubMed Abstract: Cross-reactive antibodies targeting multiple epitopes have been identified in Sarbecoviruses, but the precise molecular mechanism(s) behind the crossreactivity remain poorly understood. Here, we isolate 3D1, a broadly neutralizing antibody (bnAb) derived from a human combinatorial antibody library targeting the conserved HR1 domain. 3D1 uniquely recognizes a β-turn fold comprising a 6-mer peptide (pep) that forms during a pre-hairpin transition state, occurring exclusively before membrane fusion during viral infection. 3D1 effectively neutralizes a wide range of live SARS-CoV-2 wild-type strains except for Omicron, which evades neutralization due to a detrimental point mutation (Q954H). Notably, this cryptic epitope reveals a signature motif that extends throughout the core region of coronaviruses and is also present in various RNA viruses, including HIV and Marburgvirus. 3D1 functions as a natural or background antibody capable of binding to a diverse array of non-self antigens. 3D1's cross-reactivity underscores the effectiveness of the library approach, which encompasses the entire antibody repertoire.

PubMed: 40813592
DOI: 10.1038/s41467-025-63101-1

Experimental method

X-RAY DIFFRACTION (1.03 Å)