title: The structural basis of 5' triphosphate double-stranded RNA recognition by RIG-I C-terminal domain.
abstract: RIG-I is a cytosolic sensor of viral RNA that plays crucial roles in the induction of type I interferons. The C-terminal domain (CTD) of RIG-I is responsible for the recognition of viral RNA with 5' triphosphate (ppp). However, the mechanism of viral RNA recognition by RIG-I is still not fully understood. Here, we show that RIG-I CTD binds 5' ppp dsRNA or ssRNA, as well as blunt-ended dsRNA, and exhibits the highest affinity for 5' ppp dsRNA. Crystal structures of RIG-I CTD bound to 5' ppp dsRNA with GC- and AU-rich sequences revealed that RIG-I recognizes the termini of the dsRNA and interacts with the 5' ppp through extensive electrostatic interactions. Mutagenesis and RNA-binding studies demonstrated that similar binding surfaces are involved in the recognition of different forms of RNA. Mutations of key residues at the RNA-binding surface affected RIG-I signaling in cells.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Lu
authors.forename: Hengyu
authors.initials: H
authors.lastname: Xu
authors.forename: C T
authors.initials: CT
authors.lastname: Ranjith-Kumar
authors.forename: Monica T
authors.initials: MT
authors.lastname: Brooks
authors.forename: Tim Y
authors.initials: TY
authors.lastname: Hou
authors.forename: Fuqu
authors.initials: F
authors.lastname: Hu
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Herr
authors.forename: Roland K
authors.initials: RK
authors.lastname: Strong
authors.forename: C Cheng
authors.initials: CC
authors.lastname: Kao
authors.forename: Pingwei
authors.initials: P
authors.lastname: Li
mesh_terms: D001483:Base Sequence; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011122:Polyphosphates / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000378:metabolism*; D011971:Receptors, Immunologic; D017422:Sequence Analysis, DNA; D020349:Surface Plasmon Resonance; D014461:Ultracentrifugation
chemical_list: D011122:Polyphosphates; D012330:RNA, Double-Stranded; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; C005692:triphosphoric acid