Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, 60637, USA.
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Nat Commun. 2019 Aug 9;10(1):3629. doi: 10.1038/s41467-019-11585-z.
Picornaviral IRES elements are essential for initiating the cap-independent viral translation. However, three-dimensional structures of these elements remain elusive. Here, we report a 2.84-Å resolution crystal structure of hepatitis A virus IRES domain V (dV) in complex with a synthetic antibody fragment-a crystallization chaperone. The RNA adopts a three-way junction structure, topologically organized by an adenine-rich stem-loop motif. Despite no obvious sequence homology, the dV architecture shows a striking similarity to a circularly permuted form of encephalomyocarditis virus J-K domain, suggesting a conserved strategy for organizing the domain architecture. Recurrence of the motif led us to use homology modeling tools to compute a 3-dimensional structure of the corresponding domain of foot-and-mouth disease virus, revealing an analogous domain organizing motif. The topological conservation observed among these IRESs and other viral domains implicates a structured three-way junction as an architectural scaffold to pre-organize helical domains for recruiting the translation initiation machinery.
小核糖核酸病毒 IRES 元件对于启动帽非依赖性病毒翻译是必不可少的。然而，这些元件的三维结构仍然难以捉摸。在这里，我们报告了甲型肝炎病毒 IRES 结构域 V（dV）与合成抗体片段-结晶辅助因子复合物的 2.84Å 分辨率晶体结构。该 RNA 采用三链连接结构，拓扑结构由富含腺嘌呤的茎环模体组织。尽管没有明显的序列同源性，但 dV 结构显示出与环状排列的脑心肌炎病毒 J-K 结构域的惊人相似性，这表明了一种用于组织结构域结构的保守策略。该模体的重复使我们能够使用同源建模工具计算口蹄疫病毒相应结构域的 3 维结构，揭示了类似的结构域组织模体。这些 IRES 和其他病毒结构域之间观察到的拓扑守恒表明，具有结构化的三链连接作为一种架构支架，用于预先组织螺旋结构域以招募翻译起始机制。
