Allosteric conformational changes of human HBV core protein transform its assembly.
Allosteric conformational changes of human HBV core protein transform its assembly.
复制标题
人乙型肝炎病毒核心蛋白的变构构象变化改变了其组装
DOI：
10.1038/s41598-017-01568-9
复制
发表时间：
2017-05-03
影响因子：
4.6
通讯作者：
Yin CC
中科院分区：
文献类型：
--
作者：
Liu C;Fan G;Wang Z;Chen HS;Yin CC
乙型肝炎病毒核心蛋白（HBc）在病毒生命周期中具有多种作用：病毒组装、逆转录室、细胞内运输和核功能。HBc具有组装多态性，可以组装成二十面体衣壳和异常的非衣壳结构。装配多态性被假设是由最小的装配单元HBc二聚体的变构构象变化引起的，但控制HBc二聚体装配多态性的机制仍然是未知的。通过使用实验性抗病毒药物BAY 41-4109，我们成功地将HBc组装体从二十面体衣壳转化为螺旋管。对螺旋管、T = 4二十面体衣壳和片状HBc系综中HBc二聚体的结构分析揭示了二聚体界面内的差异。破坏HBc间二聚体界面可能会促进HBc的各种组装形式。我们的工作为HBV组装机制提供了新的结构见解，并为抗HBV药物设计提供了战略指导。
Hepatitis B Virus core protein (HBc) has multiple roles in the viral lifecycle: viral assembly, compartment for reverse transcription, intracellular trafficking, and nuclear functions. HBc displays assembly polymorphism - it can assemble into icosahedral capsid and aberrant non-capsid structures. It has been hypothesized that the assembly polymorphism is due to allosteric conformational changes of HBc dimer, the smallest assembly unit, however, the mechanism governing the polymorphic assembly of the HBc dimer is still elusive. By using the experimental antiviral drug BAY 41-4109, we successfully transformed the HBc assembly from icosahedral capsid to helical tube. Structural analyses of HBc dimers from helical tubes, T = 4 icosahedral capsid, and sheet-like HBc ensemble revealed differences within the inter-dimer interface. Disruption of the HBc inter-dimer interface may likely promote the various assembly forms of HBc. Our work provides new structural insights into the HBV assembly mechanism and strategic guide for anti-HBV drug design.