title: Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA.
abstract: RIG-I is a key innate immune pattern-recognition receptor that triggers interferon expression upon detection of intracellular 5'triphosphate double-stranded RNA (5'ppp-dsRNA) of viral origin. RIG-I comprises N-terminal caspase activation and recruitment domains (CARDs), a DECH helicase, and a C-terminal domain (CTD). We present crystal structures of the ligand-free, autorepressed, and RNA-bound, activated states of RIG-I. Inactive RIG-I has an open conformation with the CARDs sequestered by a helical domain inserted between the two helicase moieties. ATP and dsRNA binding induce a major rearrangement to a closed conformation in which the helicase and CTD bind the blunt end 5'ppp-dsRNA with perfect complementarity but incompatibly with continued CARD binding. We propose that after initial binding of 5'ppp-dsRNA to the flexibly linked CTD, co-operative tight binding of ATP and RNA to the helicase domain liberates the CARDs for downstream signaling. These findings significantly advance our molecular understanding of the activation of innate immune signaling helicases.
authors: European Molecular Biology Laboratory, Grenoble Outstation, France.
authors: Eva
authors: E
authors: Kowalinski
authors: Thomas
authors: T
authors: Lunardi
authors: Andrew A
authors: AA
authors: McCarthy
authors: Jade
authors: J
authors: Louber
authors: Joanna
authors: J
authors: Brunel
authors: Boyan
authors: B
authors: Grigorov
authors: Denis
authors: D
authors: Gerlier
authors: Stephen
authors: S
authors: Cusack
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002645:Chickens / Q000276:immunology; D004372:Ducks / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000276:immunology / Q000378:metabolism*; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000737:chemistry* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: C437968:PLAAT4 protein, human; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D051192:Receptors, Pattern Recognition; D018168:Receptors, Retinoic Acid; D000255:Adenosine Triphosphate