Poxviruses encode decapping enzymes that remove the protective 5′ cap from both host and viral mRNAs to commit transcripts for decay by the cellular exonuclease Xrn1. Decapping by these enzymes is critical for poxvirus pathogenicity by means of simultaneously suppressing host protein synthesis and limiting the accumulation of viral double-stranded RNA (dsRNA), a trigger for antiviral responses. Here we present a high-resolution structural view of the vaccinia virus decapping enzyme D9. This Nudix enzyme contains a domain organization different from other decapping enzymes in which a three-helix bundle is inserted into the catalytic Nudix domain. The 5′ mRNA cap is positioned in a bipartite active site at the interface of the two domains. Specificity for the methylated guanosine cap is achieved by stacking between conserved aromatic residues in a manner similar to that observed in canonical cap-binding proteins VP39, eIF4E, and CBP20, and distinct from eukaryotic decapping enzyme Dcp2.

痘病毒编码脱帽酶，从宿主和病毒 mRNA 上去除保护性 5' 帽，以提交转录本以供细胞外切核酸酶 Xrn1 降解。通过同时抑制宿主蛋白合成和限制病毒双链 RNA (dsRNA) 的积累，这些酶的脱盖对于痘病毒致病性至关重要，dsRNA 是抗病毒反应的触发因素。在这里，我们展示了牛痘病毒脱帽酶 D9 的高分辨率结构图。这种 Nudix 酶包含一个结构域组织，不同于其他脱帽酶，其中一个三螺旋束被插入到催化 Nudix 结构域中。5' mRNA 帽位于两个结构域界面处的二分活性位点。