8WLS

Bcl-xL in complex with HBx BH3 delta C peptide

8WLS の概要

• エントリーDOI: 10.2210/pdb8wls/pdb
• 分子名称: Bcl-2-like protein 1, Protein X (2 entities in total)
• 機能のキーワード: complex, interaction, apoptosis
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 20727.88

構造登録者

Kobayashi, N.,Nagata, T.,Kusunoki, H. (登録日: 2023-10-01, 公開日: 2024-03-20, 最終更新日: 2024-05-15)

主引用文献

Kusunoki, H.,Sakamoto, T.,Kobayashi, N.,Kohno, T.,Wakamatsu, K.,Nagata, T.
Structural Insights into the Interaction between the C-Terminal-Deleted BH3-like Motif Peptide of Hepatitis B Virus X Protein and Bcl-x L.
Biochemistry, 63:632-643, 2024

PubMed Abstract: Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV) infection. The full-length HBx protein interacts with Bcl-x and is involved in the HBV replication and cell death processes. The three hydrophobic residues Trp120, Leu123, and Ile127 of the HBx BH3-like motif are essential for the Bcl-x-binding. On the other hand, various lengths of C-terminal-truncated HBx mutants are frequently detected in HCC tissues, and these mutants, rather than the full-length HBx, appear to be responsible for HCC development. Notably, the region spanning residues 1-120 of HBx [HBx(1 and 120)] has been strongly associated with an increased risk of HCC development. However, the mode of interaction between HBx(1-120) and Bcl-x remains unclear. HBx(1-120) possesses only Trp120 among the three hydrophobic residues essential for the Bcl-x-binding. To elucidate this interaction mode, we employed a C-terminal-deleted HBx BH3-like motif peptide composed of residues 101-120. Here, we present the NMR complex structure of Bcl-x and HBx(101-120). Our results demonstrate that HBx(101-120) binds to Bcl-x in a weaker manner. Considering the high expression of Bcl-x in HCC cells, this weak interaction, in conjunction with the overexpression of Bcl-x in HCC cells, may potentially contribute to HCC development through the interaction between C-terminal-truncated HBx and Bcl-x.

PubMed: 38377677
DOI: 10.1021/acs.biochem.3c00709

実験手法

SOLUTION NMR