The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands.
The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands.
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DOI：
10.1016/j.molcel.2022.09.029
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发表时间：
2022-11-03
期刊：
影响因子：
16
通讯作者：
Pyle, Anna Marie
中科院分区：
文献类型：
--
作者：
Wang, Wenshuai;Pyle, Anna Marie
RIG-I 是一种重要的先天免疫受体，用于检测和应对 RNA 病毒感染。 RIG-I特异性识别病毒RNA分子的独特分子特征，并选择性地将它们与宿主细胞中丰富的密切相关的RNA区分开来。通过 RIG-I 与宿主和病毒 RNA 配体复合物的一系列高分辨率冷冻电镜结构揭示了这种精细选择性的物理基础。这些研究表明，RIG-I 主动对细胞质中的双链 RNA 进行采样，并通过采用两种不同类型的蛋白质折叠来区分它们。结合病毒RNA后，RIG-I采用有利于信号传导的高亲和力构象，而宿主RNA则诱导自抑制构象，刺激RNA释放。通过将蛋白质折叠与 RNA 结合选择性相结合，RIG-I 可以区分仅相差一个磷酸基团的 RNA 分子，从而解释了选择性抗病毒传感和 RIG-I 失调时诱导自身免疫的分子基础。王等人。表明 RIG-I 使用结构域解折叠事件与目标病毒配体牢固结合，并使用替代的酶促活性构象来感知和丢弃不适当的宿主配体，从而解释了选择性抗病毒传感和 RIG-I 失调时诱导自身免疫的分子基础。
RIG-I is an essential innate immune receptor for detecting and responding to infection by RNA viruses. RIG-I specifically recognizes the unique molecular features of viral RNA molecules and selectively distinguishes them from closely-related RNAs abundant in host cells. The physical basis for this exquisite selectivity is revealed through a series of high-resolution cryo-EM structures of RIG-I in complex with host and viral RNA ligands. These studies demonstrate that RIG-I actively samples double-stranded RNAs in the cytoplasm and distinguishes them by adopting two different types of protein folds. Upon binding viral RNA, RIG-I adopts a high-affinity conformation that is conducive to signaling, while host RNA induces an autoinhibited conformation that stimulates RNA release. By coupling protein folding with RNA binding selectivity, RIG-I distinguishes RNA molecules that differ by as little as one phosphate group, thereby explaining the molecular basis for selective antiviral sensing and the induction of autoimmunity upon RIG-I dysregulation. Wang et al. show that RIG-I uses a domain unfolding event to bind strongly with target viral ligands and an alternative, enzymatically active conformation for sensing and discarding inappropriate host ligands, thereby explaining the molecular basis for selective antiviral sensing and the induction of autoimmunity upon RIG-I dysregulation.
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影响因子：
64.8
作者：
Jiang, Fuguo;Ramanathan, Anand;Miller, Matthew T.;Tang, Guo-Qing;Gale, Michael, Jr.;Patel, Smita S.;Marcotrigiano, Joseph
通讯作者：
Marcotrigiano, Joseph
通过RIG-I介导的5'-二磷酸RNA识别的抗病毒药免疫。
影响因子：
64.8
作者：
Goubau, Delphine;Schlee, Martin;Deddouche, Safia;Pruijssers, Andrea J.;Zillinger, Thomas;Goldeck, Marion;Schuberth, Christine;Van der Veen, Annemarthe G.;Fujimura, Tsutomu;Rehwinkel, Jan;Iskarpatyoti, Jason A.;Barchet, Winfried;Ludwig, Janos;Dermody, Terence S.;Hartmann, Gunther;Reis e Sousa, Caetano
通讯作者：
Reis e Sousa, Caetano
DOI：
10.1107/s2059798318009324
发表时间：
2018-09-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Afonine PV;Klaholz BP;Moriarty NW;Poon BK;Sobolev OV;Terwilliger TC;Adams PD;Urzhumtsev A
通讯作者：
Urzhumtsev A
影响因子：
5.2
作者：
Cesaro T;Michiels T
通讯作者：
Michiels T
影响因子：
16
作者：
Devarkar SC;Schweibenz B;Wang C;Marcotrigiano J;Patel SS
通讯作者：
Patel SS