title: Structure and functional characterization of the RNA-binding element of the NLRX1 innate immune modulator.
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.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Minsun
authors.initials: M
authors.lastname: Hong
authors.forename: Sung-il
authors.initials: SI
authors.lastname: Yoon
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D007113:Immunity, Innate; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D012367:RNA, Viral / Q000276:immunology; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D024101:Mitochondrial Proteins; C527006:NLRX1 protein, human; D010446:Peptide Fragments; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins