The structural basis of 5' triphosphate double-stranded RNA recognition by RIG-I C-terminal domain.

The structural basis of 5' triphosphate double-stranded RNA recognition by RIG-I C-terminal domain.
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DOI:
10.1016/j.str.2010.05.007
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发表时间:
2010-08-11
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Li P
Li P
中科院分区:
其他
文献类型:
--
作者:
Lu C;Xu H;Ranjith-Kumar CT;Brooks MT;Hou TY;Hu F;Herr AB;Strong RK;Kao CC;Li P

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RIG - I是一种病毒RNA的胞质传感器,在I型干扰素的诱导中起关键作用。RIG - I的C末端结构域(CTD)负责识别具有5′三磷酸(5′ ppp)的病毒RNA。然而,RIG - I识别病毒RNA的机制仍未完全清楚。在此我们表明,RIG - I CTD结合5′ ppp双链RNA或单链RNA,以及平端双链RNA,并且对5′ ppp双链RNA表现出最高亲和力。与富含GC和富含AU序列的5′ ppp双链RNA结合的RIG - I CTD的晶体结构显示,RIG - I识别双链RNA的末端,并通过广泛的静电相互作用与5′三磷酸相互作用。诱变和RNA结合研究表明,相似的结合表面参与不同形式RNA的识别。RNA结合表面关键残基的突变影响细胞中RIG - I的信号传导。
RIG-I is a cytosolic sensor of viral RNA that plays crucial roles in the induction of type I interferons. The C-terminal domain (CTD) of RIG-I is responsible for the recognition of viral RNA with 5′ triphosphate (5′ ppp). However, the mechanism of viral RNA recognition by RIG-I is still not fully understood. Here we show that RIG-I CTD binds 5′ ppp dsRNA or ssRNA, as well as blunt-ended dsRNA, and exhibits the highest affinity for 5′ ppp dsRNA. Crystal structures of RIG-I CTD bound to 5′ ppp dsRNA with GC- and AU- rich sequences revealed that RIG-I recognizes the termini of the dsRNA and interacts with the 5′ triphosphate through extensive electrostatic interactions. Mutagenesis and RNA binding studies demonstrated that similar binding surfaces are involved in the recognition of different forms of RNA. Mutations of key residues at the RNA binding surface affected RIG-I signaling in cells.
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