8PMW

HEV gt3 P domain in complex with glycan-sensitive nAb p60.1

8PMW の概要

• エントリーDOI: 10.2210/pdb8pmw/pdb
• 分子名称: scFv_p60.1, Capsid protein, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: hev, p domain, non-glycosylated, glycan-sensitive, neutralizing antibody (nab), viral protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 198595.18

構造登録者

Ssebyatika, G.,Krey, T. (登録日: 2023-06-29, 公開日: 2024-07-10, 最終更新日: 2025-07-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.98 Å)