Chen Ke, Liao Wenjian, Wang Jiali, Ren Yangyi, Lu Zhizhong, Peng Xuemei, Wang Jia, Huang Lin
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Nucleic Acids Res. 2025 Jul 19;53(14). doi: 10.1093/nar/gkaf702.
Purine riboswitches, located in the 5'-untranslated regions of bacterial messenger RNA, regulate gene expression by sensing purines and their derivatives. A class of the guanine-I riboswitch variants was recently reported to be the third class of 2'-deoxyguanosine (2'-dG) riboswitch termed 2'-dG-III riboswitch. Here we present the crystal structures of the 2'-dG-III riboswitch bound with 2'-dG, guanosine, or guanine. Despite similarities in secondary and overall structures to other purine riboswitches, the 2'-dG-III riboswitch exhibits unique features in its loop-loop interaction, three-way junction, and ligand binding. The 2'-dG-III riboswitch exhibits a tuning fork-like structure with a unique six-tiered interaction within the three-way junction. The second, third, and fourth tiers form the ligand-binding pocket, with a consistent binding mode for the guanine moiety of all three ligands. Structural and biochemical analyses reveal detailed interactions between the 2'-dG-III riboswitch and different ligands, providing insights into its regulatory mechanisms in purine metabolism.
嘌呤核糖开关位于细菌信使核糖核酸的5'非翻译区，通过感知嘌呤及其衍生物来调节基因表达。最近报道了一类鸟嘌呤-I核糖开关变体是2'-脱氧鸟苷（2'-dG）核糖开关的第三类，称为2'-dG-III核糖开关。本文展示了与2'-dG、鸟苷或鸟嘌呤结合的2'-dG-III核糖开关的晶体结构。尽管其二级结构和整体结构与其他嘌呤核糖开关有相似之处，但2'-dG-III核糖开关在其环-环相互作用、三向连接和配体结合方面表现出独特特征。2'-dG-III核糖开关呈现出一种音叉状结构，在三向连接内具有独特的六层相互作用。第二、第三和第四层形成配体结合口袋，对所有三种配体的鸟嘌呤部分具有一致的结合模式。结构和生化分析揭示了2'-dG-III核糖开关与不同配体之间的详细相互作用，为其在嘌呤代谢中的调节机制提供了见解。
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