Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16610 Prague, Czech Republic.
Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16610 Prague, Czech Republic.
Structure. 2017 Feb 7;25(2):219-230. doi: 10.1016/j.str.2016.11.021. Epub 2017 Jan 5.
Picornaviruses are small positive-sense single-stranded RNA viruses that include many important human pathogens. Within the host cell, they replicate at specific replication sites called replication organelles. To create this membrane platform, they hijack several host factors including the acyl-CoA-binding domain-containing protein-3 (ACBD3). Here, we present a structural characterization of the molecular complexes formed by the non-structural 3A proteins from two species of the Kobuvirus genus of the Picornaviridae family and the 3A-binding domain of the host ACBD3 protein. Specifically, we present a series of crystal structures as well as a molecular dynamics simulation of the 3A:ACBD3 complex at the membrane, which reveals that the viral 3A proteins act as molecular harnesses to enslave the ACBD3 protein leading to its stabilization at target membranes. Our data provide a structural rationale for understanding how these viral-host protein complexes assemble at the atomic level and identify new potential targets for antiviral therapies.
小核糖核酸病毒是一类含有多种重要人类病原体的小型正链单链 RNA 病毒。在宿主细胞内，它们在特定的复制部位（称为复制细胞器）进行复制。为了创建这个膜平台，它们劫持了包括酰基辅酶 A 结合域蛋白 3（ACBD3）在内的几种宿主因子。在这里，我们对小核糖核酸病毒科柯萨奇病毒属的两种病毒的非结构 3A 蛋白和宿主 ACBD3 蛋白的 3A 结合域形成的分子复合物进行了结构特征描述。具体来说，我们展示了一系列晶体结构和 3A:ACBD3 复合物在膜上的分子动力学模拟，这揭示了病毒 3A 蛋白作为分子马具，奴役 ACBD3 蛋白，使其在靶膜上稳定。我们的数据为理解这些病毒-宿主蛋白复合物如何在原子水平上组装提供了结构基础，并确定了新的抗病毒治疗的潜在靶点。
