title: Toll-like receptor 8 senses degradation products of single-stranded RNA.
abstract: Toll-like receptor 8 (TLR8) recognizes viral or bacterial single-stranded RNA (ssRNA) and activates innate immune systems. TLR8 is activated by uridine- and guanosine-rich ssRNA as well as by certain synthetic chemicals; however, the molecular basis for ssRNA recognition has remained unknown. In this study, to elucidate the recognition mechanism of ssRNA, we determined the crystal structures of human TLR8 in complex with ssRNA. TLR8 recognized two degradation products of ssRNA—uridine and a short oligonucleotide—at two distinct sites: uridine bound the site on the dimerization interface where small chemical ligands are recognized, whereas short oligonucleotides bound a newly identified site on the concave surface of the TLR8 horseshoe structure. Site-directed mutagenesis revealed that both binding sites were essential for activation of TLR8 by ssRNA. These results demonstrate that TLR8 is a sensor for both uridine and a short oligonucleotide derived from RNA.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tanji
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Umeharu
authors.initials: U
authors.lastname: Ohto
authors.affiliation: 1] Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. [2] Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Department of Chemistry, Graduate School of Science and Technology, Tokyo Metropolitan University, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Taoka
authors.affiliation: Department of Chemistry, Graduate School of Science and Technology, Tokyo Metropolitan University, Tokyo, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamauchi
authors.affiliation: 1] Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan. [2] Department of Chemistry, Graduate School of Science and Technology, Tokyo Metropolitan University, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Isobe
authors.affiliation: Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyake
authors.affiliation: 1] Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan. [2] Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001665:Binding Sites; D002151:Calorimetry; D002460:Cell Line; D002853:Chromatography, Liquid; D018360:Crystallography, X-Ray; D004330:Drosophila; D006801:Humans; D013058:Mass Spectrometry; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry* / Q000378:metabolism*; D051200:Toll-Like Receptor 8 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8; D012313:RNA