Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Program in Chemistry and Chemical Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Structure. 2022 May 5;30(5):721-732.e4. doi: 10.1016/j.str.2022.02.012. Epub 2022 Mar 14.
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.
痘病毒编码去帽酶，可从宿主和病毒 mRNA 上去除保护的 5' 帽，使转录本通过细胞外切核酸酶 Xrn1 降解。这些酶的去帽作用对于痘病毒的致病性至关重要，因为它可以同时抑制宿主蛋白合成并限制病毒双链 RNA（dsRNA）的积累，dsRNA 是抗病毒反应的触发因素。在这里，我们呈现了痘病毒去帽酶 D9 的高分辨率结构视图。这种 Nudix 酶具有与其他去帽酶不同的结构域组织，其中三螺旋束插入到催化 Nudix 结构域中。5' mRNA 帽位于两个结构域界面处的二部分活性位点中。通过保守芳香族残基之间的堆积来实现对甲基化鸟苷帽的特异性，这种方式类似于在规范的帽结合蛋白 VP39、eIF4E 和 CBP20 中观察到的方式，与真核去帽酶 Dcp2 不同。
