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| | ==Crystal structure of horse TLR9 in complex with two DNAs (CpG DNA and TCGCAC DNA)== | | ==Crystal structure of horse TLR9 in complex with two DNAs (CpG DNA and TCGCAC DNA)== |
| - | <StructureSection load='5y3j' size='340' side='right' caption='[[5y3j]], [[Resolution|resolution]] 1.81Å' scene=''> | + | <StructureSection load='5y3j' size='340' side='right'caption='[[5y3j]], [[Resolution|resolution]] 1.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5y3j]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Equus_caballus Equus caballus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y3J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y3J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5y3j]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Equus_caballus Equus caballus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y3J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Y3J FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 1.81Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLR9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9796 Equus caballus])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=5y3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y3j OCA], [http://pdbe.org/5y3j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y3j RCSB], [http://www.ebi.ac.uk/pdbsum/5y3j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y3j ProSAT]</span></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=5y3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y3j OCA], [https://pdbe.org/5y3j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5y3j RCSB], [https://www.ebi.ac.uk/pdbsum/5y3j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5y3j ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TLR9_HORSE TLR9_HORSE]] 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. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (By similarity).[UniProtKB:Q9NR96]<ref>PMID:25686612</ref> | + | [https://www.uniprot.org/uniprot/TLR9_HORSE TLR9_HORSE] 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. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (By similarity).[UniProtKB:Q9NR96]<ref>PMID:25686612</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5y3j" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5y3j" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Equus caballus]] | | [[Category: Equus caballus]] |
| - | [[Category: Ishida, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Ohto, U]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Shimizu, T]] | + | [[Category: Ishida H]] |
| - | [[Category: Dna binding]] | + | [[Category: Ohto U]] |
| - | [[Category: Immune system]] | + | [[Category: Shimizu T]] |
| - | [[Category: Innate immunity]]
| + | |
| - | [[Category: Leucine-rich repeat]]
| + | |
| - | [[Category: Toll-like receptor]]
| + | |
| Structural highlights
Function
TLR9_HORSE 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. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (By similarity).[UniProtKB:Q9NR96][1]
Publication Abstract from PubMed
Toll-like receptor 9 (TLR9) recognizes DNA containing CpG motifs derived from bacteria and viruses and activates the innate immune response to eliminate them. TLR9 is known to bind to CpG DNA, and here, we identified another DNA binding site in TLR9 that binds DNA containing cytosine at the second position from the 5' end (5'-xCx DNA). 5'-xCx DNAs bound to TLR9 in the presence of CpG DNA and cooperatively promoted dimerization and activation of TLR9. Binding at both sites was important for efficient activation of TLR9. The 5'-xCx DNA bound the site corresponding to the nucleoside binding site in TLR7 and TLR8 as revealed by the structural analysis. This study revealed that TLR9 recognizes two types of DNA through its two binding sites for efficient activation. This information may contribute to the development of drugs that control the activity of TLR9.
Toll-like Receptor 9 Contains Two DNA Binding Sites that Function Cooperatively to Promote Receptor Dimerization and Activation.,Ohto U, Ishida H, Shibata T, Sato R, Miyake K, Shimizu T Immunity. 2018 Mar 24. pii: S1074-7613(18)30089-X. doi:, 10.1016/j.immuni.2018.03.013. PMID:29625894[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ohto U, Shibata T, Tanji H, Ishida H, Krayukhina E, Uchiyama S, Miyake K, Shimizu T. Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9. Nature. 2015 Apr 30;520(7549):702-5. doi: 10.1038/nature14138. Epub 2015 Feb 9. PMID:25686612 doi:http://dx.doi.org/10.1038/nature14138
- ↑ Ohto U, Ishida H, Shibata T, Sato R, Miyake K, Shimizu T. Toll-like Receptor 9 Contains Two DNA Binding Sites that Function Cooperatively to Promote Receptor Dimerization and Activation. Immunity. 2018 Mar 24. pii: S1074-7613(18)30089-X. doi:, 10.1016/j.immuni.2018.03.013. PMID:29625894 doi:http://dx.doi.org/10.1016/j.immuni.2018.03.013
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