8PMY

HEV gt3 P domain in complex with glycan-insensitive nAb p60.15

This is a non-PDB format compatible entry.

Summary for 8PMY

• Entry DOI: 10.2210/pdb8pmy/pdb
• Descriptor: scFv_p60.15, Capsid protein, ZINC ION, ... (4 entities in total)
• Functional Keywords: hev, p domain, non-glycosylated, glycan-insensitive, neutralizing antibody (nab), viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 77397.24

Authors

Ssebyatika, G.,Krey, T. (deposition date: 2023-06-29, release date: 2024-07-10, Last modification date: 2025-07-23)

Primary citation

Ssebyatika, G.,Dinkelborg, K.,Stroh, L.J.,Hinte, F.,Corneillie, L.,Hueffner, L.,Guzman, E.M.,Nankya, P.L.,Pluckebaum, N.,Fehlau, L.,Garn, J.,Meyer, N.,Prallet, S.,Mehnert, A.K.,Kraft, A.R.M.,Verhoye, L.,Jacobsen, C.,Steinmann, E.,Wedemeyer, H.,Viejo-Borbolla, A.,Dao Thi, V.L.,Pietschmann, T.,Lutgehetmann, M.,Meuleman, P.,Dandri, M.,Krey, T.,Behrendt, P.
Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice.
Nat Commun, 16:1995-1995, 2025

PubMed Abstract: Hepatitis E virus (HEV) causes 3.3 million symptomatic cases and 44,000 deaths per year. Chronic infections can arise in immunocompromised individuals, and pregnant women may suffer from fulminant disease as a consequence of HEV infection. Despite these important implications for public health, no specific antiviral treatment has been approved to date. Here, we report combined functional, biochemical, and X-ray crystallographic studies that characterize the human antibody response in convalescent HEV patients. We identified a class of potent and broadly neutralizing human antibodies (bnAbs), targeting a quaternary epitope located at the tip of the HEV capsid protein pORF2 that contains an N-glycosylation motif and is conserved across members of the Hepeviridae. These glycan-sensitive bnAbs specifically recognize the non-glycosylated pORF2 present in infectious particles but not the secreted glycosylated form acting as antibody decoy. Our most potent bnAb protects human liver-chimeric mice from intraperitoneal HEV challenge and co-housing exposure. These results provide insights into the bnAb response to this important emerging pathogen and support the development of glycan-sensitive antibodies to combat HEV infection.

PubMed: 40011441
DOI: 10.1038/s41467-025-57182-1

Experimental method

X-RAY DIFFRACTION (2.406 Å)