title: Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response.
abstract: RNA recognition receptors are important for detection of and response to viral infections. RIG-I and MDA5 are cytoplasmic DEX(D/H) helicase proteins that can induce signaling in response to RNA ligands, including those from viral infections. LGP2, a homolog of RIG-I and MDA5 without the caspase recruitment domain required for signaling, plays an important role in modulating signaling by MDA5 and RIG-I, presumably through heterocomplex formation and/or by serving as a sink for RNAs. Here we demonstrate that LGP2 can be coexpressed with RIG-I to inhibit activation of the NF-kappaB reporter expression and that LGP2 protein produced in insect cells can bind both single- and double-stranded RNA (dsRNA), with higher affinity and cooperativity for dsRNA. Electron microscopy and image reconstruction were used to determine the shape of the LGP2 monomer in the absence of dsRNA and of the dimer complexed to a 27-bp dsRNA. LGP2 has striking structural similarity to the helicase domain of the superfamily 2 DNA helicase, Hef.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Ayaluru
authors.initials: A
authors.lastname: Murali
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.forename: C T
authors.initials: CT
authors.lastname: Ranjith-Kumar
authors.forename: Kanchan
authors.initials: K
authors.lastname: Bhardwaj
authors.forename: Andreas
authors.initials: A
authors.lastname: Holzenburg
authors.forename: Pingwei
authors.initials: P
authors.lastname: Li
authors.forename: C Cheng
authors.initials: CC
authors.lastname: Kao
mesh_terms: D000818:Animals; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D000072640:Interferon-Induced Helicase, IFIH1; 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; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D018411:Spodoptera; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship; D014777:Virus Diseases / Q000235:genetics / Q000378:metabolism
chemical_list: C437968:PLAAT4 protein, human; D012330:RNA, Double-Stranded; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; C520569:DHX58 protein, human; C452815:IFIH1 protein, human; D004265:DNA Helicases; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases