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| | <StructureSection load='4r08' size='340' side='right'caption='[[4r08]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='4r08' size='340' side='right'caption='[[4r08]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4r08]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R08 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R08 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4r08]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R08 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UCG:3-O-[(R)-{[(2R,3AR,4R,6R,6AR)-6-(2-AMINO-6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)-2-HYDROXY-2-OXIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4-YL]METHOXY}(HYDROXY)PHOSPHORYL]URIDINE+5-(DIHYDROGEN+PHOSPHATE)'>UCG</scene>, <scene name='pdbligand=URI:URIDINE'>URI</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UCG:3-O-[(R)-{[(2R,3AR,4R,6R,6AR)-6-(2-AMINO-6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)-2-HYDROXY-2-OXIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4-YL]METHOXY}(HYDROXY)PHOSPHORYL]URIDINE+5-(DIHYDROGEN+PHOSPHATE)'>UCG</scene>, <scene name='pdbligand=URI:URIDINE'>URI</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r07|4r07]], [[4r09|4r09]], [[4r0a|4r0a]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r08 OCA], [https://pdbe.org/4r08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r08 RCSB], [https://www.ebi.ac.uk/pdbsum/4r08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r08 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLR8, UNQ249/PRO286 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4r08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r08 OCA], [http://pdbe.org/4r08 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r08 RCSB], [http://www.ebi.ac.uk/pdbsum/4r08 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r08 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TLR8_HUMAN 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.<ref>PMID:17932028</ref> | + | [https://www.uniprot.org/uniprot/TLR8_HUMAN 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.<ref>PMID:17932028</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Toll-like Receptors|Toll-like Receptors]] | + | *[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ohto, U]] | + | [[Category: Ohto U]] |
| - | [[Category: Shimizu, T]] | + | [[Category: Shimizu T]] |
| - | [[Category: Tanji, H]] | + | [[Category: Tanji H]] |
| - | [[Category: Antitumor drug binding]]
| + | |
| - | [[Category: Antiviral binding]]
| + | |
| - | [[Category: Glycosylation]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Innate immunity]]
| + | |
| - | [[Category: Leucine rich repeat]]
| + | |
| - | [[Category: Rna binding]]
| + | |
| - | [[Category: Rna receptor]]
| + | |
| - | [[Category: Rna recognition]]
| + | |
| Structural highlights
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.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Doyle SL, Jefferies CA, Feighery C, O'Neill LA. Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase. J Biol Chem. 2007 Dec 21;282(51):36953-60. Epub 2007 Oct 11. PMID:17932028 doi:10.1074/jbc.M707682200
- ↑ Tanji H, Ohto U, Shibata T, Taoka M, Yamauchi Y, Isobe T, Miyake K, Shimizu T. Toll-like receptor 8 senses degradation products of single-stranded RNA. Nat Struct Mol Biol. 2015 Feb;22(2):109-15. doi: 10.1038/nsmb.2943. Epub 2015 Jan, 19. PMID:25599397 doi:http://dx.doi.org/10.1038/nsmb.2943
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