Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses

被引：393

作者：

Takahasi, Kiyohiro ^{[1
]}

Yoneyama, Mitsutoshi ^{[2
,3
,5
]}

Nishihori, Tatsuya ^{[1
]}

Hirai, Reiko ^{[2
,3
]}

Kumeta, Hiroyuki ^{[1
]}

Narita, Ryo ^{[2
,3
]}

Gale, Michael, Jr. ^{[4
]}

Inagaki, Fuyuhiko ^{[1
]}

Fujita, Takashi ^{[2
,3
]}

机构：

[1] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Biol Struct, Sapporo, Hokkaido 0600812, Japan

[2] Kyoto Univ, Inst Virus Res, Mol Genet Lab, Kyoto 6068507, Japan

[3] Kyoto Univ, Grad Sch Biostudies, Mol Cell Biol Lab, Kyoto 6068507, Japan

[4] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA

[5] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan

来源：

MOLECULAR CELL | 2008年 / 29卷 / 04期

关键词：

D O I：

10.1016/j.molcel.2007.11.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A DExD/H protein, RIG-1, is critical in innate antiviral responses by sensing viral RNA. Here we show that RIG-I recognizes two distinct viral RNA patterns: double-stranded (ds) and 5'ppp single-stranded (ss) RNA. The binding of RIG-I with dsRNA or 5'ppp ssRNA in the presence of ATP produces a common structure, as suggested by protease digestion. Further analyses demonstrated that the C-terminal domain of RIG-I (CTD) recognizes these RNA patterns and CTD coincides with the autorepression domain. Structural analysis of CTD by NMR spectroscopy in conjunction with mutagenesis revealed that the basic surface of CTD with a characteristic cleft interacts with RIG-I ligands. Our results suggest that the bipartite structure of CTD regulates RIG-I on encountering viral RNA patterns.

引用

页码：428 / 440

页数：13

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