How RIG-I like receptors activate MAVS.
RIG-I and MDA5 are well-conserved cytoplasmic pattern recognition receptors that detect viral RNAs during infection and activate the type I interferon (IFN)-mediated antiviral immune response. While much is known about how these receptors recognize viral RNAs, how they interact with their common signaling adaptor molecule MAVS and activate the downstream signaling pathway had been less clear. Previous studies have shown that the signaling domains (tandem CARDs or 2CARDs) of RIG-I and MDA5 must form homo-oligomers in order to interact with MAVS, and that their interactions lead to filament formation of MAVS, a pre-requisite for downstream signal activation. More recent data suggest that multiple mechanisms synergistically promote tetramer formation of RIG-I 2CARD, and that this tetramer resembles a lock-washer, which serves as a helical template to nucleate the MAVS filament. We here summarize these recent findings and discuss the current understanding of the signal activation mechanisms of RIG-I and MDA5.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, United States; Program in Cellular and Molecular Medicine, Boston Children's Hospital, United States.
Bin
B
Wu
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, United States; Program in Cellular and Molecular Medicine, Boston Children's Hospital, United States. Electronic address: Sun.Hur@childrens.harvard.edu.
Sun
S
Hur
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D012367:RNA, Viral / Q000378:metabolism; D011971:Receptors, Immunologic; D051192:Receptors, Pattern Recognition / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D007370:Interferon Type I; C505371:MAVS protein, human; D012367:RNA, Viral; D011971:Receptors, Immunologic; D051192:Receptors, Pattern Recognition; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases