3vq1: Difference between revisions

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<StructureSection load='3vq1' size='340' side='right'caption='[[3vq1]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
<StructureSection load='3vq1' size='340' side='right'caption='[[3vq1]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3vq1]] is a 4 chain structure with sequence from [https://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=3VQ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VQ1 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3vq1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VQ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VQ1 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=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]] 2.7&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3vq2|3vq2]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tlr4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Md2 ([https://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=3vq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vq1 OCA], [https://pdbe.org/3vq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vq1 RCSB], [https://www.ebi.ac.uk/pdbsum/3vq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vq1 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=3vq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vq1 OCA], [https://pdbe.org/3vq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vq1 RCSB], [https://www.ebi.ac.uk/pdbsum/3vq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vq1 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[https://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.  
[https://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 ==
[[https://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> [[https://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).
[https://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>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: Ohto, U]]
[[Category: Ohto U]]
[[Category: Shimizu, T]]
[[Category: Shimizu T]]
[[Category: Glycosylation]]
[[Category: Immune system]]
[[Category: Leucine rich repeat md-2 related lipid recognition]]
[[Category: Lipid binding]]
[[Category: Receptor innate immunity]]
[[Category: Secreted]]

Latest revision as of 15:31, 8 November 2023

Crystal structure of mouse TLR4/MD-2/lipid IVa complexCrystal structure of mouse TLR4/MD-2/lipid IVa complex

Structural highlights

3vq1 is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.7Å
Ligands:, ,
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]

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[2]

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

See Also

References

  1. ↑ 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
  2. ↑ Ohto U, Fukase K, Miyake K, Shimizu T. Structural basis of species-specific endotoxin sensing by innate immune receptor TLR4/MD-2. Proc Natl Acad Sci U S A. 2012 Apr 24. PMID:22532668 doi:10.1073/pnas.1201193109

3vq1, resolution 2.70Å

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