Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses

Mol Cell. 2008 Feb 29;29(4):428-40. doi: 10.1016/j.molcel.2007.11.028. Epub 2008 Jan 31.

Abstract

A DExD/H protein, RIG-I, is critical in innate antiviral responses by sensing viral RNA. Here we show that RIG-I recognizes two distinct viral RNA patterns: double-stranded (ds) and 5'ppp single-stranded (ss) RNA. The binding of RIG-I with dsRNA or 5'ppp ssRNA in the presence of ATP produces a common structure, as suggested by protease digestion. Further analyses demonstrated that the C-terminal domain of RIG-I (CTD) recognizes these RNA patterns and CTD coincides with the autorepression domain. Structural analysis of CTD by NMR spectroscopy in conjunction with mutagenesis revealed that the basic surface of CTD with a characteristic cleft interacts with RIG-I ligands. Our results suggest that the bipartite structure of CTD regulates RIG-I on encountering viral RNA patterns.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / chemistry
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Gene Expression Regulation
  • Humans
  • Immune System / physiology*
  • Interferon Regulatory Factor-3 / chemistry
  • Interferon Regulatory Factor-3 / genetics
  • Interferon Regulatory Factor-3 / metabolism
  • Interferons / immunology
  • Mice
  • Mice, Knockout
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation*
  • Oligonucleotides / chemistry
  • Oligonucleotides / genetics
  • Oligonucleotides / immunology
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • RNA, Double-Stranded / chemistry
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / immunology
  • RNA, Viral / chemistry*
  • RNA, Viral / genetics
  • RNA, Viral / immunology*
  • Sequence Alignment

Substances

  • Interferon Regulatory Factor-3
  • Oligonucleotides
  • RNA, Double-Stranded
  • RNA, Viral
  • Interferons
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases

Associated data

  • PDB/2RMJ