View source for 4r09


==Crystal structure of human TLR8 in complex with ORN06S==
<StructureSection load='4r09' size='340' side='right'caption='[[4r09]], [[Resolution|resolution]] 2.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4r09]] 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=4R09 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R09 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.62&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=06S:O-[(2R,3S,4R,5R)-5-(2-AMINO-6-OXO-3,6-DIHYDRO-9H-PURIN-9-YL)-2-({[(S)-({(2R,3S,4R,5R)-5-(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)-4-HYDROXY-2-[(THIOPHOSPHONOOXY)METHYL]TETRAHYDROFURAN-3-YL}OXY)(SULFANYL)PHOSPHORYL]OXY}METHYL)-4-HYDROXYTETRAHYDROFURAN-3-YL]+DIHYDROGEN+(S)-PHOSPHOROTHIOATE'>06S</scene>, <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=UPT:1-[(2R,3AR,4R,6R,6AR)-2-HYDROXY-6-(HYDROXYMETHYL)-2-SULFIDOTETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-4-YL]PYRIMIDINE-2,4(1H,3H)-DIONE'>UPT</scene>, <scene name='pdbligand=URI:URIDINE'>URI</scene></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=4r09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r09 OCA], [https://pdbe.org/4r09 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r09 RCSB], [https://www.ebi.ac.uk/pdbsum/4r09 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r09 ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== 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<ref>PMID:25599397</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4r09" style="background-color:#fffaf0;"></div>

==See Also==
*[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ohto U]]
[[Category: Shimizu T]]
[[Category: Tanji H]]