Structure and functional characterization of the RNA-binding element of the NLRX1 innate immune modulator

Immunity. 2012 Mar 23;36(3):337-47. doi: 10.1016/j.immuni.2011.12.018. Epub 2012 Mar 1.

Abstract

Mitochondrial NLRX1 is a member of the family of nucleotide-binding domain and leucine-rich-repeat-containing proteins (NLRs) that mediate host innate immunity as intracellular surveillance sensors against common molecular patterns of invading pathogens. NLRX1 functions in antiviral immunity, but the molecular mechanism of its ligand-induced activation is largely unknown. The crystal structure of the C-terminal fragment (residues 629-975) of human NLRX1 (cNLRX1) at 2.65 Å resolution reveals that cNLRX1 consists of an N-terminal helical (LRRNT) domain, central leucine-rich repeat modules (LRRM), and a C-terminal three-helix bundle (LRRCT). cNLRX1 assembles into a compact hexameric architecture that is stabilized by intersubunit and interdomain interactions of LRRNT and LRRCT in the trimer and dimer components of the hexamer, respectively. Furthermore, we find that cNLRX1 interacts directly with RNA and supports a role for NLRX1 in recognition of intracellular viral RNA in antiviral immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Immunity, Innate*
  • Mitochondrial Proteins / chemistry*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / immunology*
  • Models, Molecular
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Protein Interaction Domains and Motifs
  • Protein Structure, Quaternary
  • RNA, Viral / immunology
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / immunology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology

Substances

  • Mitochondrial Proteins
  • NLRX1 protein, human
  • Peptide Fragments
  • RNA, Viral
  • RNA-Binding Proteins
  • Recombinant Proteins

Associated data

  • PDB/3UN9