RIG-I Uses an ATPase-Powered Translocation-Throttling Mechanism for Kinetic Proofreading of RNAs and Oligomerization.
RIG-I Uses an ATPase-Powered Translocation-Throttling Mechanism for Kinetic Proofreading of RNAs and Oligomerization.
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DOI：
10.1016/j.molcel.2018.08.021
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发表时间：
2018-10-18
期刊：
影响因子：
16
通讯作者：
Patel SS
中科院分区：
文献类型：
--
作者：
Devarkar SC;Schweibenz B;Wang C;Marcotrigiano J;Patel SS
RIG-I具有从胞质自身RNA库中特异性选择用于活化的病毒5 'ppp dsRNA的显著能力。RIG-I的ATP酶活性在RNA识别和激活中起作用，但其机制尚不清楚。使用瞬态动力学，我们已经阐明了ATP酶驱动的“动力学校正”机制RIG-I的激活和RNA的歧视，类似于DNA聚合酶，核糖体，和T细胞受体。即使在RIG-I的自抑制状态下，C-末端结构域也通过快速解离速率在动力学上区分自身RNA。ATP结合促进dsRNA参与，但有趣的是使RIG-I混杂，解释了Singleton-Merton综合征相关突变体结合ATP而不水解的组成性信号传导。ATP水解使自身RNA比5 'ppp dsRNA更快地解离，但更重要的是，通过易位驱动RIG-I寡聚化，我们表明这是由解旋酶基序-IVa调节的。RIG-I从dsRNA-末端定向易位到茎区和5 'ppp-末端“节流”易位，以提供穿线和构建信号活性寡聚复合物的机制。
RIG-I has a remarkable ability to specifically select viral 5’ppp dsRNAs for activation from a pool of cytosolic self-RNAs. The ATPase activity of RIG-I plays a role in RNA discrimination and activation, but the underlying mechanism was unclear. Using transient state kinetics, we have elucidated the ATPase-driven ‘kinetic proofreading’ mechanism of RIG-I activation and RNA discrimination, akin to DNA polymerases, ribosomes, and T-cell receptors. Even in the autoinhibited state of RIG-I, the C-terminal domain kinetically discriminates against self-RNAs by fast off-rates. ATP-binding facilitates dsRNA engagement, but interestingly makes RIG-I promiscuous, explaining the constitutive signaling by Singleton-Merton syndrome-linked mutants that bind ATP without hydrolysis. ATP hydrolysis dissociates self-RNAs faster than 5’ppp dsRNA, but more importantly, drives RIG-I oligomerization through translocation, that we show is regulated by helicase motif-IVa. RIG-I translocates directionally from dsRNA-end into stem-region and 5’ppp-end “throttles” translocation to provide a mechanism for threading and building a signaling-active oligomeric complex.
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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
影响因子：
14.9
作者：
Lu C;Ranjith-Kumar CT;Hao L;Kao CC;Li P
通讯作者：
Li P
影响因子：
64.8
作者：
Peisley A;Wu B;Xu H;Chen ZJ;Hur S
通讯作者：
Hur S
DOI：
10.1074/jbc.m109.089912
发表时间：
2010-06-25
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Nistal-Villán E;Gack MU;Martínez-Delgado G;Maharaj NP;Inn KS;Yang H;Wang R;Aggarwal AK;Jung JU;García-Sastre A
通讯作者：
García-Sastre A
影响因子：
5.7
作者：
Banerjee, Kinshuk;Kolomeisky, Anatoly B.;Igoshin, Oleg A.
通讯作者：
Igoshin, Oleg A.