乙型肝炎病毒剪接蛋白(Hepatits B Spliced Protein, HBSP) 可导致肝细胞凋亡，但其作用机制尚未阐明。我们前期研究结果显示HBSP蛋白以寡聚体形式存在，通过pull-down发现HBSP与BCL-2家族成员BCL-xL存在着非常强的相互作用。推测二者在促肝细胞凋亡过程中共同发挥着重要作用，但这种相互作用的结构基础不明。本项目拟通过解析HBSP蛋白、HBSP-BCL-xL复合物蛋白的三维晶体结构，并结合生物化学及细胞生物学的研究，揭示HBSP中BH3结构域与BCL-xL相互作用的结构基础，深入阐明HBSP诱导肝细胞凋亡的分子机理。

The Hepatitis B Spliced Protein (HBSP) is one of the most important pathogenic factors of Hepatitis B virus (HBV),leads to hepatocyte apoptosis. However, the mechanisms involved is far from been fully elucidated. In our previuous study, we found that HBSP exsited in oligomer form, and interacted with BCL-xL by pull down assay,the latter was one member of BCL-2 family which was pointed to the involvement of the mitochondria-dependent apoptotic pathway. The interaction of HBSP with the antiapoptotic members palys an important role in hepatocyte apoptosis, yet the exact mechanisms remain to be fully elucidated. This proposal plans to solve the crystal structures of HBSP and HBSP-BCL-xL complex. The structural information, combined with biochemistry and cell biology study results, will help to discover the molecular mechanism of BH3 domain from HBSP in hepatocyte apoptosis. To investigate the potential role of HBSP-BCL-xL interaction in hepatocyte apoptosis, the critical motif based on the stucture of HBSP will be expolred. Our studies will provide the molecular basis and new clues for the better understanding of the HBV viral proteins involved in hepatocyte apoptosis and HBV pathogenicity.