A loosened gating mechanism of RIG-I leads to autoimmune disorders
文献类型：期刊论文
| 作者 | Lei, Yixuan1,2; Fei, Panyu3,4,7; Song, Bin2; Shi, Wenjia2,10; Luo, Cheng3,4,9,11 ; Luo, Dahai8; Li, Dan1; Chen, Wei3,4,5,6; Zheng, Jie2,10,11
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| 刊名 | NUCLEIC ACIDS RESEARCH
 |
| 出版日期 | 2022-06-10 |
| 卷号 | 50期号:10页码:5850-5863 |
| ISSN号 | 0305-1048 |
| DOI | 10.1093/nar/gkac361 |
| 文献子类 | Article |
| 英文摘要 | DDX58 encodes RIG-I, a cytosolic RNA sensor that ensures immune surveillance of nonself RNAs. Individuals with RIG-I-E510V and RIG-I-Q517H mutations have increased susceptibility to Singleton-Merten syndrome (SMS) defects, resulting in tissue-specific (mild) and classic (severe) phenotypes. The coupling between RNA recognition and conformational changes is central to RIG-I RNA proofreading, but the molecular determinants leading to dissociated disease phenotypes remain unknown. Herein, we employed hydrogen/deuterium exchange mass spectrometry (HDX-MS) and single molecule magnetic tweezers (MT) to precisely examine how subtle conformational changes in the helicase insertion domain (HEL2i) promote impaired ATPase and erroneous RNA proofreading activities. We showed that the mutations cause a loosened latch-gate engagement in apo RIG-I, which in turn gradually dampens its self RNA (Cap2 moiety:m7G cap and N1-2-2 '-O-methylation RNA) proofreading ability, leading to increased immunopathy. These results reveal HEL2i as a unique checkpoint directing two specialized functions, i.e. stabilizing the CARD2-HEL2i interface and gating the helicase from incoming self RNAs; thus, these findings add new insights into the role of HEL2i in the control of antiviral innate immunity and autoimmunity diseases. |
| WOS关键词 | DOUBLE-STRANDED-RNA ; STRUCTURAL BASIS ; RECOGNITION ; ACTIVATION ; EXCHANGE ; MUTATIONS ; REVEALS ; COMPLEX ; BINDING ; IFIH1 |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000799450100001 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309345]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Dan; Chen, Wei; Zheng, Jie |
| 作者单位 | 1.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China; 2.Chinese Acad Sci, Drug Res Ctr Immunol Dis, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Zhejiang Univ, Sch Med, Dept Cell Biol, Affiliated Hosp 2, Hangzhou 310058, Peoples R China; 4.Zhejiang Univ, Sch Med, Dept Cardiol, Affiliated Hosp 2, Hangzhou 310058, Peoples R China; 5.Zhejiang Univ, Med Ctr, Liangzhu Lab, 1369 West Wenyi Rd, Hangzhou 311121, Peoples R China; 6.Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, MOE Frontier Sci Ctr Brain Sci & Brain Machine In, State Key Lab Modern Opt Instrumentat,Key Lab Bio, Hangzhou 310058, Zhejiang, Peoples R China; 7.Zhejiang Univ, Sch Mech Engn, Hangzhou 310027, Zhejiang, Peoples R China; 8.Nanyang Technol Univ, Lee Kong Chian Sch Med, NTU Inst Struct Biol, Sch Biol Sci, Singapore 636921, Singapore; 9.Chinese Acad Sci, Chem Biol Ctr, Drug Discovery & Design Ctr, State Key Lab Drug Res,Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 10.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Jiangsu, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Lei, Yixuan,Fei, Panyu,Song, Bin,et al. A loosened gating mechanism of RIG-I leads to autoimmune disorders[J]. NUCLEIC ACIDS RESEARCH,2022,50(10):5850-5863. |
| APA | Lei, Yixuan.,Fei, Panyu.,Song, Bin.,Shi, Wenjia.,Luo, Cheng.,...&Zheng, Jie.(2022).A loosened gating mechanism of RIG-I leads to autoimmune disorders.NUCLEIC ACIDS RESEARCH,50(10),5850-5863. |
| MLA | Lei, Yixuan,et al."A loosened gating mechanism of RIG-I leads to autoimmune disorders".NUCLEIC ACIDS RESEARCH 50.10(2022):5850-5863. |
入库方式： OAI收割
来源：上海药物研究所
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