title: The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA.
abstract: The RIG-I-like receptors (RLRs), RIG-I and MDA5, recognize single-stranded RNA with 5' triphosphates and double-stranded RNA (dsRNA) to initiate innate antiviral immune responses. LGP2, a homolog of RIG-I and MDA5 that lacks signaling capability, regulates the signaling of the RLRs. To establish the structural basis of dsRNA recognition by the RLRs, we have determined the 2.0-A resolution crystal structure of human LGP2 C-terminal domain bound to an 8-bp dsRNA. Two LGP2 C-terminal domain molecules bind to the termini of dsRNA with minimal contacts between the protein molecules. Gel filtration chromatography and analytical ultracentrifugation demonstrated that LGP2 binds blunt-ended dsRNA of different lengths, forming complexes with 2:1 stoichiometry. dsRNA with protruding termini bind LGP2 and RIG-I weakly and do not stimulate the activation of RIG-I efficiently in cells. Surprisingly, full-length LGP2 containing mutations that abolish dsRNA binding retained the ability to inhibit RIG-I signaling.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A & M University, College Station, Texas 77843-2128.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biology and the Multidisciplinary Biochemistry Program, Indiana University, Bloomington, Indiana 47405.
authors.forename: C T
authors.initials: CT
authors.lastname: Ranjith-Kumar
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524.
authors.forename: Monica T
authors.initials: MT
authors.lastname: Brooks
authors.affiliation: Department of Biology and the Multidisciplinary Biochemistry Program, Indiana University, Bloomington, Indiana 47405.
authors.forename: S
authors.initials: S
authors.lastname: Dharmaiah
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Herr
authors.affiliation: Department of Biology and the Multidisciplinary Biochemistry Program, Indiana University, Bloomington, Indiana 47405.
authors.forename: Cheng
authors.initials: C
authors.lastname: Kao
authors.affiliation: Department of Biochemistry and Biophysics, Texas A & M University, College Station, Texas 77843-2128. Electronic address: pingwei@tamu.edu.
authors.forename: Pingwei
authors.initials: P
authors.lastname: Li
mesh_terms: D018360:Crystallography, X-Ray; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D009154:Mutation; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D020365:RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: C437968:PLAAT4 protein, human; D012330:RNA, Double-Stranded; D018168:Receptors, Retinoic Acid; C520569:DHX58 protein, human; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases