4r0a

Crystal structure of human TLR8 in complex with uridine mononucleoside

spinqualitylabelsall models 4r0a, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4r0a is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BMA, NAG, URI, MAN Related: 4r07, 4r08, 4r09 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TLR8_HUMAN] Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Publication Abstract from PubMed 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. Toll-like receptor 8 senses degradation products of single-stranded RNA.,Tanji H, Ohto U, Shibata T, Taoka M, Yamauchi Y, Isobe T, Miyake K, Shimizu T Nat Struct Mol Biol. 2015 Feb;22(2):109-15. doi: 10.1038/nsmb.2943. Epub 2015 Jan, 19. PMID:25599397 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Toll-like Receptors

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