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3wpg

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Revision as of 17:19, 9 March 2017

Crystal structure of mouse TLR9 in complex with inhibitory DNA4084 (form 1)

Structural highlights

3wpg is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3wpb, 3wpc, 3wpd, 3wpe, 3wpf, 3wph, 3wpi
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

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/3wpg"

@@ Line 1: / Line 1: @@
 ==Crystal structure of mouse TLR9 in complex with inhibitory DNA4084 (form 1)==
 <StructureSection load='3wpg' size='340' side='right' caption='[[3wpg]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </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>
 <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='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://www.rcsb.org/pdb/explore.do?structureId=3wpg RCSB], [http://www.ebi.ac.uk/pdbsum/3wpg PDBsum]</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>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3wpg" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Toll-like Receptors|Toll-like Receptors]]
 == References ==
 <references/>

3wpg

From Proteopedia

Revision as of 17:19, 9 March 2017

Crystal structure of mouse TLR9 in complex with inhibitory DNA4084 (form 1)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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