4K7F

Newly identified epitope V60 from HBV core protein complexed with HLA-A*0201

4K7F の概要

• エントリーDOI: 10.2210/pdb4k7f/pdb
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Core protein, ... (4 entities in total)
• 機能のキーワード: host-virus interaction, immune response, disease mutation, viral replication, ig-like domain, immune system, tcr, membrane glycoprotein, viral capsid protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 89595.67

構造登録者

Meng, S.D.,Zhang, Y.,Wu, Y.,Qi, J.X. (登録日: 2013-04-17, 公開日: 2013-06-05, 最終更新日: 2024-11-20)

主引用文献

Zhang, Y.,Ren, Y.,Wu, Y.,Zhao, B.,Qiu, L.,Li, X.,Xu, D.,Liu, J.,Gao, G.F.,Meng, S.
The L60V variation in hepatitis B virus core protein elicits new epitope-specific cytotoxic T lymphocytes and enhances viral replication.
J.Virol., 87:8075-8084, 2013

PubMed Abstract: Mutations in the core protein (HBc) of hepatitis B virus (HBV) are associated with aggressive hepatitis and advanced liver diseases in chronic hepatitis B (CHB). In this study, we identified the L60V variation in HBc that generates a new HLA-A2-restricted CD8(+) T cell epitope by screening an overlapping 9-mer peptide pool covering HBc and its variants. The nonameric epitope V60 was determined by structural and immunogenic analysis. The HBc L60V variation is correlated with hepatic necroinflammation and higher viral levels, and it may be associated with a poor prognosis in CHB patients. Immunization with the defined HBV epitope V60 peptide elicited specific cytotoxic T lymphocyte (CTL)-induced liver injury in HLA-A2(+) HBV transgenic mice. In addition, in vitro and in vivo experiments both demonstrated that the HBc L60V variation facilitates viral capsid assembly and increases HBV replication. These data suggest that the HBc L60V variation can impact both HBV replication and HBV-specific T cell responses. Therefore, our work provides further dissection of the impact of the HBc L60V variation, which orchestrates HBV replication, viral persistence, and immunopathogenesis during chronic viral infection.

PubMed: 23678186
DOI: 10.1128/JVI.00577-13

実験手法

X-RAY DIFFRACTION (2 Å)