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5ijd

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Revision as of 07:20, 3 June 2020

The crystal structure of mouse TLR4/MD-2/lipid A complex

Structural highlights

5ijd is a 4 chain structure with sequence from Bdellostoma burgeri and Lk3 transgenic mice. This structure supersedes the now removed PDB entry 5hg6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	5ljb, 5ljc
Gene:	VLRB (Bdellostoma burgeri), Ly96, Esop1, Md2 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TLR4_MOUSE] Note=The protein is encoded by the Lps locus, an important susceptibility locus, influencing the propensity to develop a disseminated Gram-negative infection.

Function

[TLR4_MOUSE] Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity).^[1] [LY96_MOUSE] Cooperates with TLR4 in the innate immune response to bacterial lipopolysaccharide (LPS), and with TLR2 in the response to cell wall components from Gram-positive and Gram-negative bacteria. Enhances TLR4-dependent activation of NF-kappa-B. Cells expressing both MD2 and TLR4, but not TLR4 alone, respond to LPS (By similarity).

Publication Abstract from PubMed

Structurally disparate molecules reportedly engage and activate Toll-like receptor (TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by dissimilar ligands remain unknown. We describe Neoseptins, chemically synthesized peptidomimetics that bear no structural similarity to the established TLR4 ligand, lipopolysaccharide (LPS), but productively engage the mouse TLR4 (mTLR4)/myeloid differentiation factor 2 (MD-2) complex. Neoseptin-3 activates mTLR4/MD-2 independently of CD14 and triggers canonical myeloid differentiation primary response gene 88 (MyD88)- and Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)-dependent signaling. The crystal structure mTLR4/MD-2/Neoseptin-3 at 2.57-A resolution reveals that Neoseptin-3 binds as an asymmetrical dimer within the hydrophobic pocket of MD-2, inducing an active receptor complex similar to that induced by lipid A. However, Neoseptin-3 and lipid A form dissimilar molecular contacts to achieve receptor activation; hence strong TLR4/MD-2 agonists need not mimic LPS.

TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS.,Wang Y, Su L, Morin MD, Jones BT, Whitby LR, Surakattula MM, Huang H, Shi H, Choi JH, Wang KW, Moresco EM, Berger M, Zhan X, Zhang H, Boger DL, Beutler B Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):E884-93. doi:, 10.1073/pnas.1525639113. Epub 2016 Feb 1. PMID:26831104^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rhee SH, Hwang D. Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF kappa B and expression of the inducible cyclooxygenase. J Biol Chem. 2000 Nov 3;275(44):34035-40. PMID:10952994 doi:10.1074/jbc.M007386200
↑ Wang Y, Su L, Morin MD, Jones BT, Whitby LR, Surakattula MM, Huang H, Shi H, Choi JH, Wang KW, Moresco EM, Berger M, Zhan X, Zhang H, Boger DL, Beutler B. TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS. Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):E884-93. doi:, 10.1073/pnas.1525639113. Epub 2016 Feb 1. PMID:26831104 doi:http://dx.doi.org/10.1073/pnas.1525639113

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ijd"

@@ Line 1: / Line 1: @@
 ==The crystal structure of mouse TLR4/MD-2/lipid A complex==
-<StructureSection load='5ijd' size='340' side='right' caption='[[5ijd]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='5ijd' size='340' side='right'caption='[[5ijd]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ijd]] is a 4 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5hg6 5hg6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IJD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IJD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ijd]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bdellostoma_burgeri Bdellostoma burgeri] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5hg6 5hg6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IJD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IJD FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=LP4:2-DEOXY-3-O-[(3R)-3-HYDROXYTETRADECANOYL]-2-{[(3R)-3-HYDROXYTETRADECANOYL]AMINO}-4-O-PHOSPHONO-BETA-D-GLUCOPYRANOSE'>LP4</scene>, <scene name='pdbligand=LP5:(R)-((2R,3S,4R,5R,6R)-3-HYDROXY-2-(HYDROXYMETHYL)-5-((R)-3-HYDROXYTETRADECANAMIDO)-6-(PHOSPHONOOXY)TETRAHYDRO-2H-PYRAN-4-YL)+3-HYDROXYTETRADECANOATE'>LP5</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=LP4:2-DEOXY-3-O-[(3R)-3-HYDROXYTETRADECANOYL]-2-{[(3R)-3-HYDROXYTETRADECANOYL]AMINO}-4-O-PHOSPHONO-BETA-D-GLUCOPYRANOSE'>LP4</scene>, <scene name='pdbligand=LP5:(R)-((2R,3S,4R,5R,6R)-3-HYDROXY-2-(HYDROXYMETHYL)-5-((R)-3-HYDROXYTETRADECANAMIDO)-6-(PHOSPHONOOXY)TETRAHYDRO-2H-PYRAN-4-YL)+3-HYDROXYTETRADECANOATE'>LP5</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ljb|5ljb]], [[5ljc|5ljc]]</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=5ijd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ijd OCA], [http://pdbe.org/5ijd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ijd RCSB], [http://www.ebi.ac.uk/pdbsum/5ijd PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VLRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7764 Bdellostoma burgeri]), Ly96, Esop1, Md2 ([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'>[http://proteopedia.org/fgij/fg.htm?mol=5ijd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ijd OCA], [http://pdbe.org/5ijd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ijd RCSB], [http://www.ebi.ac.uk/pdbsum/5ijd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ijd ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 </div>
 <div class="pdbe-citations 5ijd" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]]
+*[[Variable lymphocyte receptor 3D structures|Variable lymphocyte receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Bdellostoma burgeri]]
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Berger, M]]
 [[Category: Beutler, B]]

5ijd

From Proteopedia

Revision as of 07:20, 3 June 2020

The crystal structure of mouse TLR4/MD-2/lipid A complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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