4r0a

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(Difference between revisions)

Revision as of 09:20, 24 April 2019

Crystal structure of human TLR8 in complex with uridine mononucleoside

Structural highlights

4r0a is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	4r07, 4r08, 4r09
Gene:	TLR8, UNQ249/PRO286 (HUMAN)
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 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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4r0a"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human TLR8 in complex with uridine mononucleoside==
-<StructureSection load='4r0a' size='340' side='right' caption='[[4r0a]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='4r0a' size='340' side='right'caption='[[4r0a]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4r0a]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R0A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R0A FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4r0a]] is a 1 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=4R0A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R0A 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=URI:URIDINE'>URI</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
+</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=URI:URIDINE'>URI</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r07|4r07]], [[4r08|4r08]], [[4r09|4r09]]</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=4r0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r0a OCA], [http://pdbe.org/4r0a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r0a RCSB], [http://www.ebi.ac.uk/pdbsum/4r0a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r0a ProSAT]</span></td></tr>
 </table>
@@ Line 26: / Line 27: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Ohto, U]]
 [[Category: Shimizu, T]]

4r0a

From Proteopedia

Revision as of 09:20, 24 April 2019

Crystal structure of human TLR8 in complex with uridine mononucleoside

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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