title: Structural insights into RNA recognition by RIG-I.
abstract: Intracellular RIG-I-like receptors (RLRs, including RIG-I, MDA-5, and LGP2) recognize viral RNAs as pathogen-associated molecular patterns (PAMPs) and initiate an antiviral immune response. To understand the molecular basis of this process, we determined the crystal structure of RIG-I in complex with double-stranded RNA (dsRNA). The dsRNA is sheathed within a network of protein domains that include a conserved "helicase" domain (regions HEL1 and HEL2), a specialized insertion domain (HEL2i), and a C-terminal regulatory domain (CTD). A V-shaped pincer connects HEL2 and the CTD by gripping an α-helical shaft that extends from HEL1. In this way, the pincer coordinates functions of all the domains and couples RNA binding with ATP hydrolysis. RIG-I falls within the Dicer-RIG-I clade of the superfamily 2 helicases, and this structure reveals complex interplay between motor domains, accessory mechanical domains, and RNA that has implications for understanding the nanomechanical function of this protein family and other ATPases more broadly.
authors: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
authors: Dahai
authors: D
authors: Luo
authors: Steve C
authors: SC
authors: Ding
authors: Adriana
authors: A
authors: Vela
authors: Andrew
authors: A
authors: Kohlway
authors: Brett D
authors: BD
authors: Lindenbach
authors: Anna Marie
authors: AM
authors: Pyle
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000737:chemistry* / Q000378:metabolism; D011971:Receptors, Immunologic; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D012330:RNA, Double-Stranded; D011971:Receptors, Immunologic; D000255:Adenosine Triphosphate; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases