ArticleNucleic acids research2025
Crystal structures reveal the distinct features of the 2'-dG-III riboswitch in the purine riboswitch family.
Ke Chen, Wenjian Liao, Jiali Wang, Yangyi Ren, Zhizhong Lu, Xuemei Peng, Jia Wang, Lin Huang
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Ke ChenGuangdong 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.ORCID 0009-0005-1868-1056 Wenjian LiaoGuangdong 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.ORCID 0000-0001-9823-9949 Jiali WangGuangdong 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.
Yangyi RenGuangdong 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.ORCID 0009-0006-0959-2008 Zhizhong LuGuangdong 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.
Xuemei PengGuangdong 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.
Jia WangCollege of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China.
Lin HuangGuangdong 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.ORCID 0000-0002-2121-365X Funding
Guangdong Science and Technology Department 2020B1212030004Guangdong Science and Technology Department 2023B1212060013Guangdong Science and Technology Department 2024A1515012594Key Realm R&D Program of Guangdong Province 2022B0202050003National Natural Science Foundation of China 32001639National Natural Science Foundation of China 32171191National Natural Science Foundation of China 32400021Shenzhen Bay Scholars Program
6 · The paper itselfAbstract
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.
Indexed as
DeoxyguanosineRiboswitchRNA, BacterialBinding SitesCrystallography, X-RayGuanineGuanosineLigandsModels, MolecularNucleic Acid ConformationPurinesDeoxyguanosineGuanineGuanosineLigandspurinePurinesRiboswitchRNA, Bacterial
Identifiers
PMID40694847
PMCPMC12282948
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