Conway J F, Cheng N, Zlotnick A, Wingfield P T, Stahl S J, Steven A C
Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature. 1997 Mar 6;386(6620):91-4. doi: 10.1038/386091a0.
Despite the development of vaccines, the hepatitis B virus remains a major cause of human liver disease. The virion consists of a lipoprotein envelope surrounding an icosahedral capsid composed of dimers of a 183-residue protein, 'core antigen' (HBcAg). Knowledge of its structure is important for the design of antiviral drugs, but it has yet to be determined. Residues 150-183 are known to form a protamine-like domain required for packaging RNA, and residues 1-149 form the 'assembly domain' that polymerizes into capsids and, unusually for a capsid protein, is highly alpha-helical. Density maps calculated from cryo-electron micrographs show that the assembly domain dimer is T-shaped: its stem constitutes the dimer interface and the tips of its arms make the polymerization contacts. By refining the procedures used to calculate the map, we have extended the resolution to 9 A, revealing major elements of secondary structure. In particular, the stem, which protrudes as a spike on the capsid's outer surface, is a 4-helix bundle, formed by the pairing of alpha-helical hairpins from both subunits.
尽管已经研发出了疫苗，但乙型肝炎病毒仍然是人类肝脏疾病的主要病因。病毒粒子由脂蛋白包膜包围着一个二十面体衣壳组成，该衣壳由一种183个氨基酸残基的蛋白质“核心抗原”（HBcAg）的二聚体构成。了解其结构对于抗病毒药物的设计很重要，但尚未确定。已知150 - 183位残基形成包装RNA所需的鱼精蛋白样结构域，而1 - 149位残基形成“组装结构域”，该结构域聚合成衣壳，并且与衣壳蛋白不同寻常的是，它具有高度的α螺旋结构。从冷冻电子显微照片计算得到的密度图显示，组装结构域二聚体呈T形：其茎构成二聚体界面，其臂的末端进行聚合接触。通过改进用于计算图谱的程序，我们将分辨率提高到了9埃，揭示了二级结构的主要元件。特别是，作为衣壳外表面上的一个尖峰突出的茎是一个4螺旋束，由两个亚基的α螺旋发夹配对形成。
