Department of Research on Blood and Biological Products, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama-shi, Tokyo 208-0011, Japan.
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.
Biochem Biophys Res Commun. 2014 Jul 18;450(1):741-5. doi: 10.1016/j.bbrc.2014.06.042. Epub 2014 Jun 17.
Hepatitis B virus X protein (HBx) is a multifunctional protein, which is considered to be an essential molecule for viral replication and the development of liver diseases. Recently, it has been demonstrated that HBx can directly interact with Bcl-2 and Bcl-xL through a sequence (termed the BH3-like motif) that is related to the BH3 motif of pro-apoptotic BH3-only proteins. Here, we present the first structural characterization of the HBx BH3-like motif by circular dichroism and NMR spectroscopies. Our results demonstrated that the HBx BH3-like motif has the ability to form an α-helix, and the potential helical region involves residues L108-L134. This is a common characteristic among the BH3 peptides of pro-apoptotic BH3-only proteins, implying that HBx may interact with Bcl-2 and Bcl-xL, by forming an α-helix, similar to the interaction mode of other BH3 peptides with Bcl-2 and Bcl-xL.
乙型肝炎病毒 X 蛋白 (HBx) 是一种多功能蛋白，被认为是病毒复制和肝脏疾病发展的必需分子。最近，已经证明 HBx 可以通过与促凋亡 BH3 仅蛋白的 BH3 基序相关的序列（称为 BH3 样基序）直接与 Bcl-2 和 Bcl-xL 相互作用。在这里，我们通过圆二色性和 NMR 光谱首次对 HBx BH3 样基序进行了结构表征。我们的结果表明，HBx BH3 样基序具有形成α-螺旋的能力，潜在的螺旋区域涉及残基 L108-L134。这是促凋亡 BH3 仅蛋白的 BH3 肽的共同特征，这意味着 HBx 可能通过形成α-螺旋与 Bcl-2 和 Bcl-xL 相互作用，类似于其他 BH3 肽与 Bcl-2 和 Bcl-xL 的相互作用模式。
