ATP-dependent effector-like functions of RIG-I-like receptors.

ATP-dependent effector-like functions of RIG-I-like receptors.
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RIG-I样受体的ATP依赖性效应子样函数。

DOI:
10.1016/j.molcel.2015.03.014
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发表时间:
2015-05-07
期刊:
影响因子:
16
通讯作者:
Hur, Sun
Hur, Sun
中科院分区:
生物学1区
文献类型:
--
作者:
Yao, Hui;Dittmann, Meike;Peisley, Alys;Hoffmann, Hans-Heinrich;Gilmore, Rachel H.;Schmidt, Tobias;Schmid-Burgk, Jonathan L.;Hornung, Veit;Rice, Charles M.;Hur, Sun

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脊椎动物的抗病毒天然免疫系统通常被认为由两组不同的蛋白质组成:模式识别受体(PRRs),它检测病毒感染并诱导干扰素(IFN)信号,以及直接作用于对抗病毒复制的效应器。因此,以前对PRRs的研究,如RIG-I和MDA5,主要集中在它们在病毒双链RNA(DsRNA)检测和随后的抗病毒信号转导中的功能。我们在这里报道,RIG-I和MDA5都能有效地置换预先结合到dsRNA上的病毒蛋白,这种方式依赖于它们的ATP水解,并且这种活性有助于依赖dsRNA的抗病毒效应蛋白PKR,并允许RIG-I促进MDA5信号转导。此外,截短的RIG-I/MDA5缺乏信号域,从而具有干扰素的刺激活性,以依赖于ATP的方式取代病毒蛋白并抑制某些病毒的复制。因此,这项研究揭示了RIG-I和MDA5的新的“效应器样”功能,挑战了传统的PRRs观点。
The vertebrate antiviral innate immune system is often considered to consist of two distinct groups of proteins: pattern recognition receptors (PRRs) that detect viral infection and induce the interferon (IFN) signaling, and effectors that directly act against viral replication. Accordingly, previous studies on PRRs, such as RIG-I and MDA5, have primarily focused on their functions in viral double-stranded RNA (dsRNA) detection and consequent antiviral signaling. We here report that both RIG-I and MDA5 efficiently displace viral proteins pre-bound to dsRNA in a manner dependent on their ATP hydrolysis, and that this activity assists a dsRNA-dependent antiviral effector protein, PKR, and allows RIG-I to promote MDA5 signaling. Furthermore, truncated RIG-I/MDA5 lacking the signaling domain, and hence the IFN stimulatory activity, displace viral proteins and suppress replication of certain viruses in an ATP-dependent manner. Thus, this study reveals novel “effector-like” functions of RIG-I and MDA5 that challenge the conventional view of PRRs.
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