ATP Hydrolysis Enhances RNA Recognition and Antiviral Signal Transduction by the Innate Immune Sensor, Laboratory of Genetics and Physiology 2 (LGP2)
ATP Hydrolysis Enhances RNA Recognition and Antiviral Signal Transduction by the Innate Immune Sensor, Laboratory of Genetics and Physiology 2 (LGP2)
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DOI：
10.1074/jbc.m112.424416
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发表时间：
2013-01-11
影响因子：
4.8
通讯作者：
Horvath, Curt M.
中科院分区：
文献类型：
--
作者：
Bruns, Annie M.;Pollpeter, Darja;Horvath, Curt M.
遗传学和生理学实验室2（LGP 2）是细胞质模式识别受体的RIG-I样受体家族的成员，其检测病毒感染的分子特征并启动抗病毒信号转导级联。LGP 2的ATP水解活性对于抗病毒信号传导是必不可少的，但LGP 2的酶性质如何调节其生物学反应尚不清楚。对LGP 2的dsRNA结合和酶活性的定量分析揭示了高的不依赖dsRNA的ATP水解活性。LGP 2和突变体的生化测定和单分子分析，从dsRNA刺激的ATP水解解离基础证明，LGP 2利用基础ATP水解，以提高和多样化其RNA识别能力，使蛋白质与内在穷人的基板。这种性质是LGP 2与另一种RIG-I样受体MDA 5协同作用所必需的，以在脑心肌炎病毒感染或用poly（I：C）转染期间增强IFN β的体内转录。这些结果证明了以前未被认识到的LGP 2 ATP水解和RNA相互作用的特性，并为LGP 2在抗病毒信号传导中的积极调节作用提供了机制基础。
Laboratory of genetics and physiology 2 (LGP2) is a member of the RIG-I-like receptor family of cytoplasmic pattern recognition receptors that detect molecular signatures of virus infection and initiate antiviral signal transduction cascades. The ATP hydrolysis activity of LGP2 is essential for antiviral signaling, but it has been unclear how the enzymatic properties of LGP2 regulate its biological response. Quantitative analysis of the dsRNA binding and enzymatic activities of LGP2 revealed high dsRNA-independent ATP hydrolysis activity. Biochemical assays and single-molecule analysis of LGP2 and mutant variants that dissociate basal from dsRNA-stimulated ATP hydrolysis demonstrate that LGP2 utilizes basal ATP hydrolysis to enhance and diversify its RNA recognition capacity, enabling the protein to associate with intrinsically poor substrates. This property is required for LGP2 to synergize with another RIG-I-like receptor, MDA5, to potentiate IFN beta transcription in vivo during infection with encephalomyocarditis virus or transfection with poly(I: C). These results demonstrate previously unrecognized properties of LGP2 ATP hydrolysis and RNA interaction and provide a mechanistic basis for a positive regulatory role for LGP2 in antiviral signaling.