Abstract：
Capsid-like poxvirus scaffold proteins self-assemble into semi-regular lattice that govern the formation of spherical immature virus particles. The scaffolding is a critical step in virus morphogenesis as exemplified by the drug rifampicin that impairs the recruitment of scaffold onto the viral membrane in vaccinia virus (VACV). Here we report cryo-electron microscopy structure of scaffolding protein Orfv075 of orf virus (ORFV) that causes smallpox-like diseases in sheep, goats and occasionally humans via zoonotic infection. We demonstrate that the regions that are involved in intertrimeric interactions for scaffold assembly are largely conserved in comparison to its VACV orthologue protein D13 whose intermediate assembly structures have been previously characterized. By contrast, less conserved regions are located away from these interfaces, indicating both viruses share similar assembly mechanisms. We also show that the phenylalanine-rich binding site of rifampicin in D13 is conserved in Orfv075, and molecular docking simulation confirms similar binding modes. Our study provides structural basis of scaffolding protein as a target for anti-poxvirus treatment across wide range of poxvirus genera.
摘要：
衣壳样痘病毒支架蛋白自组装成半规则晶格，控制球形未成熟病毒颗粒的形成。支架是病毒形态发生中的关键步骤，例如利福平药物，该药物会损害牛痘病毒（VACV）中支架在病毒膜上的募集。在这里，我们报告了引起绵羊天花样疾病的orf病毒（ORFV）的支架蛋白Orfv075的低温电子显微镜结构，山羊和偶尔通过人畜共患感染的人类。我们证明，与其VACV直向同源蛋白D13相比，参与支架组装的三聚体间相互作用的区域在很大程度上是保守的，其中间组装结构已被先前表征。相比之下,保守程度较低的区域位于远离这些界面的位置，表明这两种病毒共享相似的程序集机制。我们还表明，D13中利福平的富含苯丙氨酸的结合位点在Orfv075中是保守的，分子对接模拟证实了类似的结合模式。我们的研究提供了支架蛋白作为跨多种痘病毒属的抗痘病毒治疗靶标的结构基础。
