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| | ==Crystal structure of human TLR8 in complex with Resiquimod (R848) crystal form 1== | | ==Crystal structure of human TLR8 in complex with Resiquimod (R848) crystal form 1== |
| - | <StructureSection load='3w3l' size='340' side='right' caption='[[3w3l]], [[Resolution|resolution]] 2.33Å' scene=''> | + | <StructureSection load='3w3l' size='340' side='right'caption='[[3w3l]], [[Resolution|resolution]] 2.33Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3w3l]] 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=3W3L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W3L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3w3l]] 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=3W3L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W3L 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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RX8:1-[4-AMINO-2-(ETHOXYMETHYL)-1H-IMIDAZO[4,5-C]QUINOLIN-1-YL]-2-METHYLPROPAN-2-OL'>RX8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.33Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3w3g|3w3g]], [[3w3j|3w3j]], [[3w3k|3w3k]], [[3w3m|3w3m]], [[3w3n|3w3n]]</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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RX8:1-[4-AMINO-2-(ETHOXYMETHYL)-1H-IMIDAZO[4,5-C]QUINOLIN-1-YL]-2-METHYLPROPAN-2-OL'>RX8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=3w3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w3l OCA], [https://pdbe.org/3w3l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w3l RCSB], [https://www.ebi.ac.uk/pdbsum/3w3l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w3l ProSAT]</span></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=3w3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w3l OCA], [http://pdbe.org/3w3l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3w3l RCSB], [http://www.ebi.ac.uk/pdbsum/3w3l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3w3l 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: Ohto, U]] | + | [[Category: Large Structures]] |
| - | [[Category: Shimizu, T]] | + | [[Category: Ohto U]] |
| - | [[Category: Tanji, H]] | + | [[Category: Shimizu T]] |
| - | [[Category: Antivirus and antitumor drug]] | + | [[Category: Tanji H]] |
| - | [[Category: Antivirus and antitumor drug binding]]
| + | |
| - | [[Category: Glycosylation]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Innate immunity]]
| + | |
| - | [[Category: Leucine rich repeat]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Resiquimod]]
| + | |
| - | [[Category: Rna]]
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| - | [[Category: Rna binding]]
| + | |
| - | [[Category: Rna receptor]]
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| - | [[Category: Rna recognition]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Ssrna]]
| + | |
| Structural highlights
3w3l is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.33Å |
| Ligands: | , , , , |
| 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.[1]
Publication Abstract from PubMed
Toll-like receptor 7 (TLR7) and TLR8 recognize single-stranded RNA and initiate innate immune responses. Several synthetic agonists of TLR7-TLR8 display novel therapeutic potential; however, the molecular basis for ligand recognition and activation of signaling by TLR7 or TLR8 is largely unknown. In this study, the crystal structures of unliganded and ligand-induced activated human TLR8 dimers were elucidated. Ligand recognition was mediated by a dimerization interface formed by two protomers. Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity. The loop between leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization. Thus, ligand binding induces reorganization of the TLR8 dimer, which enables downstream signaling processes.
Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands.,Tanji H, Ohto U, Shibata T, Miyake K, Shimizu T Science. 2013 Mar 22;339(6126):1426-9. doi: 10.1126/science.1229159. PMID:23520111[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, Miyake K, Shimizu T. Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands. Science. 2013 Mar 22;339(6126):1426-9. doi: 10.1126/science.1229159. PMID:23520111 doi:http://dx.doi.org/10.1126/science.1229159
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