Molecular Imprinting as a Signal-Activation Mechanism of the Viral RNA Sensor RIG-I

被引：196

作者：

Wu, Bin ^{[1
,3
]}

Peisley, Alys ^{[1
,3
]}

Tetrault, David ^{[4
,5
]}

Li, Zongli ^{[2
,7
]}

Egelman, Edward H. ^{[6
]}

Magor, Katharine E. ^{[4
,5
]}

Walz, Thomas ^{[2
,7
]}

Penczek, Pawel A. ^{[8
]}

Hur, Sun ^{[1
,3
]}

机构：

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[3] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA

[4] Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada

[5] Univ Alberta, Li Ka Shing Inst Virol, Edmonton, AB T6G 2E9, Canada

[6] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA

[7] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[8] Univ Texas Houston, Houston Med Sch, Dept Biochem & Mol Biol, Houston, TX 77030 USA

来源：

MOLECULAR CELL | 2014年 / 55卷 / 04期

关键词：

STRUCTURAL BASIS; RECOGNITION; FILAMENTS; OLIGOMERIZATION;

D O I：

10.1016/j.molcel.2014.06.010

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：

RIG-I activates interferon signaling pathways by promoting filament formation of the adaptor molecule, MAVS. Assembly of the MAVS filament is mediated by its CARD domain (CARD(MAVS)), and requires its interaction with the tandem CARDs of RIG-I (2CARD(RIG-I)). However, the precise nature of the interaction between 2CARD(RIG-I) and CARD(MAVS), and how this interaction leads to CARD(MAVS) filament assembly, has been unclear. Here we report a 3.6 angstrom electron microscopy structure of the CARD(MAVS) filament and a 3.4 angstrom crystal structure of the 2CARD(RIG-I):CARD(MAVS) complex, representing 2CARD(RIG-I) "caught in the act" of nucleating the CARD MAVS filament. These structures, together with functional analyses, show that 2CARD(RIG-I) acts as a template for the CARD(MAVS) filament assembly, by forming a helical tetrameric structure and recruiting CARD(MAVS) along its helical trajectory. Our work thus reveals that signal activation by RIG-I occurs by imprinting its helical assembly architecture on MAVS, a previously uncharacterized mechanism of signal transmission.

引用

页码：511 / 523

页数：13

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