3vq2
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal structure of mouse TLR4/MD-2/LPS complex== | |
| - | + | <StructureSection load='3vq2' size='340' side='right' caption='[[3vq2]], [[Resolution|resolution]] 2.48Å' scene=''> | |
| - | { | + | == Structural highlights == |
| - | + | <table><tr><td colspan='2'>[[3vq2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VQ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VQ2 FirstGlance]. <br> | |
| - | ==Disease== | + | </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> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3vq1|3vq1]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tlr4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Md2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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=3vq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vq2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vq2 RCSB], [http://www.ebi.ac.uk/pdbsum/3vq2 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[http://www.uniprot.org/uniprot/TLR4_MOUSE 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. | [[http://www.uniprot.org/uniprot/TLR4_MOUSE 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 == | |
| - | ==Function== | + | |
[[http://www.uniprot.org/uniprot/TLR4_MOUSE 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).<ref>PMID:10952994</ref> [[http://www.uniprot.org/uniprot/LY96_MOUSE 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). | [[http://www.uniprot.org/uniprot/TLR4_MOUSE 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).<ref>PMID:10952994</ref> [[http://www.uniprot.org/uniprot/LY96_MOUSE 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). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Lipopolysaccharide (LPS), also known as endotoxin, activates the innate immune response through toll-like receptor 4 (TLR4) and its coreceptor, MD-2. MD-2 has a unique hydrophobic cavity that directly binds to lipid A, the active center of LPS. Tetraacylated lipid IVa, a synthetic lipid A precursor, acts as a weak agonist to mouse TLR4/MD-2, but as an antagonist to human TLR4/MD-2. However, it remains unclear as to how LPS and lipid IVa show agonistic or antagonistic activities in a species-specific manner. The present study reports the crystal structures of mouse TLR4/MD-2/LPS and TLR4/MD-2/lipid IVa complexes at 2.5 and 2.7 A resolutions, respectively. Mouse TLR4/MD-2/LPS exhibited an agonistic "m"-shaped 2:2:2 complex similar to the human TLR4/MD-2/LPS complex. Mouse TLR4/MD-2/lipid IVa complex also showed an agonistic structural feature, exhibiting architecture similar to the 2:2:2 complex. Remarkably, lipid IVa in the mouse TLR4/MD-2 complex occupied nearly the same space as LPS, although lipid IVa lacked the two acyl chains. Human MD-2 binds lipid IVa in an antagonistic manner completely differently from the way mouse MD-2 does. Together, the results provide structural evidence of the agonistic property of lipid IVa on mouse TLR4/MD-2 and deepen understanding of the ligand binding and dimerization mechanism by the structurally diverse LPS variants. | ||
| - | + | Structural basis of species-specific endotoxin sensing by innate immune receptor TLR4/MD-2.,Ohto U, Fukase K, Miyake K, Shimizu T Proc Natl Acad Sci U S A. 2012 Apr 24. PMID:22532668<ref>PMID:22532668</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
| - | [[Category: Ohto, U | + | [[Category: Ohto, U]] |
| - | [[Category: Shimizu, T | + | [[Category: Shimizu, T]] |
[[Category: Glycosylation]] | [[Category: Glycosylation]] | ||
[[Category: Immune system]] | [[Category: Immune system]] | ||
Revision as of 06:40, 21 December 2014
Crystal structure of mouse TLR4/MD-2/LPS complex
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