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Hepatitis B virus X protein （HBx）plays a crucial role in the developmentof hepatocellular carcinoma （HCC） associated with hepatitis B virus（HBV） infection. The full-length HBx protein interacts with Bcl-xL and is involved in the HBV replication and cell death processes.The three hydrophobic residues Trp120, Leu123, and Ile127 of the HBxBH3-like motif are essential for the Bcl-xL-binding. Onthe other hand, various lengths of C-terminal-truncated HBx mutantsare frequently detected in HCC tissues, and these mutants, ratherthan the full-length HBx, appear to be responsible for HCC development.Notably, the region spanning residues 1–120 of HBx [HBx-（1 and120）] has been strongly associated with an increased risk of HCC development.However, the mode of interaction between HBx（1–120） and Bcl-xL remains unclear. HBx（1–120） possesses only Trp120among the three hydrophobic residues essential for the Bcl-xL-binding. To elucidate this interaction mode, we employed a C-terminal-deletedHBx BH3-like motif peptide composed of residues 101–120. Here,we present the NMR complex structure of Bcl-xL and HBx（101–120）.Our results demonstrate that HBx（101–120） binds to Bcl-xL in a weaker manner. Considering the high expression of Bcl-xL in HCC cells, this weak interaction, in conjunction withthe overexpression of Bcl-xL in HCC cells, may potentiallycontribute to HCC development through the interaction between C-terminal-truncatedHBx and Bcl-xL.
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