7YI6

bnAb 3D1 in complex with 6-mer HR1 peptide from HCoV-229E S protein

Summary for 7YI6

• Entry DOI: 10.2210/pdb7yi6/pdb
• Descriptor: Spike glycoprotein, light chain of 3D1, heavy chain of 3D1, ... (7 entities in total)
• Functional Keywords: bnab, hr1, 6-mer, antiviral protein, antiviral protein-immune system complex, antiviral protein/immune system
• Biological source: Human coronavirus 229E (HCoV-229E); More
• Total number of polymer chains: 6
• Total formula weight: 93657.22

Authors

Yan, L.,Yang, G. (deposition date: 2022-07-15, release date: 2023-08-30, 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 (2.28 Å)