期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 415, 期 1, 页码 75-81出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2011.10.015
关键词
RIG-I; Virus; Interferon
资金
- Ministry of Education, Science, Sports and Culture, Japan
- Ministry of Health. Labor and Welfare
- PRESTO Japan Science and Technology Agency
- Uehara Memorial Foundation
- Takeda Science Foundation
- Nippon Boehringer Ingelheim
- Grants-in-Aid for Scientific Research [23770113, 20112009, 23390108] Funding Source: KAKEN
In virus-infected cells, viral RNA with non-self structural pattern is recognized by DExD/Hbox RNA helicase, RIG-I. Once RIG-I senses viral RNA, it triggers a signaling cascade, resulting in the activation of genes including type I interferon, which activates antiviral responses. Overexpression of N-terminal caspase activation and recruitment domain (CARD) is sufficient to activate signaling; however basal activity of full-length RIG-I is undetectable. The repressor domain (RD), initially identified as a.a. 735-925, is responsible for diminished basal activity; therefore, it is suggested that RIG-I is under auto-repression in uninfected cells and the repression is reversed upon its encounter with viral RNA. In this report, we further delimited RD to a.a. 747-801, which corresponds to a linker connecting the helicase and the C-terminal domain (CTD). Alanine substitutions of the conserved residues in the linker conferred constitutive activity to full-length RIG-I. We found that the constitutive active mutants do not exhibit ATPase activity, suggesting that ATPase is required for de-repression but not signaling itself. Furthermore, trypsin digestion of recombinant RIG-I revealed that the wild-type, but not linker mutant conforms to the trypsin-resistant structure, containing CARD and helicase domain. The result strongly suggests that the linker is responsible for maintaining RIG-I in a closed structure to minimize unwanted production of interferon in uninfected cells. These findings shed light on the structural regulation of RIG-I function. (C) 2011 Elsevier Inc. All rights reserved.
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