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| | ==Crystal structure of mouse TLR9 in complex with inhibitory DNA4084 (form 1)== | | ==Crystal structure of mouse TLR9 in complex with inhibitory DNA4084 (form 1)== |
| - | <StructureSection load='3wpg' size='340' side='right' caption='[[3wpg]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='3wpg' size='340' side='right'caption='[[3wpg]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3wpg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WPG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WPG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3wpg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=3WPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WPG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.246Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3wpb|3wpb]], [[3wpc|3wpc]], [[3wpd|3wpd]], [[3wpe|3wpe]], [[3wpf|3wpf]], [[3wph|3wph]], [[3wpi|3wpi]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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">Tlr9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3wpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wpg OCA], [https://pdbe.org/3wpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wpg RCSB], [https://www.ebi.ac.uk/pdbsum/3wpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wpg 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=3wpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wpg OCA], [http://pdbe.org/3wpg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wpg RCSB], [http://www.ebi.ac.uk/pdbsum/3wpg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wpg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TLR9_MOUSE TLR9_MOUSE]] 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. Plays a role in defense against systemic mouse cytomegalovirus infection. Controls lymphocyte response to Helicobacter infection.<ref>PMID:14993594</ref> <ref>PMID:17474149</ref> | + | [https://www.uniprot.org/uniprot/TLR9_MOUSE TLR9_MOUSE] 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. Plays a role in defense against systemic mouse cytomegalovirus infection. Controls lymphocyte response to Helicobacter infection.<ref>PMID:14993594</ref> <ref>PMID:17474149</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: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Ohto, U]] | + | [[Category: Mus musculus]] |
| - | [[Category: Shimizu, T]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Cpg motif]] | + | [[Category: Ohto U]] |
| - | [[Category: Dna binding]] | + | [[Category: Shimizu T]] |
| - | [[Category: Dna binding protein-dna complex]]
| + | |
| - | [[Category: Glycosylation]]
| + | |
| - | [[Category: Innate immunity]]
| + | |
| - | [[Category: Leucine rich repeat]]
| + | |
| - | [[Category: Receptor]]
| + | |
| Structural highlights
Function
TLR9_MOUSE 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. Plays a role in defense against systemic mouse cytomegalovirus infection. Controls lymphocyte response to Helicobacter infection.[1] [2]
Publication Abstract from PubMed
Innate immunity serves as the first line of defence against invading pathogens such as bacteria and viruses. Toll-like receptors (TLRs) are examples of innate immune receptors, which sense specific molecular patterns from pathogens and activate immune responses. TLR9 recognizes bacterial and viral DNA containing the cytosine-phosphate-guanine (CpG) dideoxynucleotide motif. The molecular basis by which CpG-containing DNA (CpG-DNA) elicits immunostimulatory activity via TLR9 remains to be elucidated. Here we show the crystal structures of three forms of TLR9: unliganded, bound to agonistic CpG-DNA, and bound to inhibitory DNA (iDNA). Agonistic-CpG-DNA-bound TLR9 formed a symmetric TLR9-CpG-DNA complex with 2:2 stoichiometry, whereas iDNA-bound TLR9 was a monomer. CpG-DNA was recognized by both protomers in the dimer, in particular by the amino-terminal fragment (LRRNT-LRR10) from one protomer and the carboxy-terminal fragment (LRR20-LRR22) from the other. The iDNA, which formed a stem-loop structure suitable for binding by intramolecular base pairing, bound to the concave surface from LRR2-LRR10. This structure serves as an important basis for improving our understanding of the functional mechanisms of TLR9.
Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9.,Ohto U, Shibata T, Tanji H, Ishida H, Krayukhina E, Uchiyama S, Miyake K, Shimizu T Nature. 2015 Apr 30;520(7549):702-5. doi: 10.1038/nature14138. Epub 2015 Feb 9. PMID:25686612[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, Mudd S, Shamel L, Sovath S, Goode J, Alexopoulou L, Flavell RA, Beutler B. Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3516-21. Epub 2004 Mar 1. PMID:14993594 doi:http://dx.doi.org/10.1073/pnas.0400525101
- ↑ Anderson AE, Worku ML, Khamri W, Bamford KB, Walker MM, Thursz MR. TLR9 polymorphisms determine murine lymphocyte responses to Helicobacter: results from a genome-wide scan. Eur J Immunol. 2007 Jun;37(6):1548-61. PMID:17474149 doi:http://dx.doi.org/10.1002/eji.200636562
- ↑ 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
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