2z64: Difference between revisions

Latest revision as of 08:08, 23 October 2024

Crystal structure of mouse TLR4 and mouse MD-2 complex

Structural highlights

2z64 is a 2 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 2.84Å
Ligands:	BMA, FUL, NAG
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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

TLR4 and MD-2 form a heterodimer that recognizes LPS (lipopolysaccharide) from Gram-negative bacteria. Eritoran is an analog of LPS that antagonizes its activity by binding to the TLR4-MD-2 complex. We determined the structure of the full-length ectodomain of the mouse TLR4 and MD-2 complex. We also produced a series of hybrids of human TLR4 and hagfish VLR and determined their structures with and without bound MD-2 and Eritoran. TLR4 is an atypical member of the LRR family and is composed of N-terminal, central, and C-terminal domains. The beta sheet of the central domain shows unusually small radii and large twist angles. MD-2 binds to the concave surface of the N-terminal and central domains. The interaction with Eritoran is mediated by a hydrophobic internal pocket in MD-2. Based on structural analysis and mutagenesis experiments on MD-2 and TLR4, we propose a model of TLR4-MD-2 dimerization induced by LPS.

Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran.,Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO Cell. 2007 Sep 7;130(5):906-17. PMID:17803912^[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
↑ Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO. Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell. 2007 Sep 7;130(5):906-17. PMID:17803912 doi:https://dx.doi.org/10.1016/j.cell.2007.08.002

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OCA

[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] Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO. Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell. 2007 Sep 7;130(5):906-17. PMID:17803912 doi:https://dx.doi.org/10.1016/j.cell.2007.08.002

[1]

[2]

@@ Line 3: / Line 3: @@
 <StructureSection load='2z64' size='340' side='right'caption='[[2z64]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2z64]] is a 2 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=2Z64 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z64 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2z64]] is a 2 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=2Z64 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z64 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</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]] 2.84&#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;'>[[2z62|2z62]], [[2z63|2z63]], [[2z65|2z65]], [[2z66|2z66]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</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=2z64 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z64 OCA], [https://pdbe.org/2z64 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2z64 RCSB], [https://www.ebi.ac.uk/pdbsum/2z64 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2z64 ProSAT]</span></td></tr>
 </table>
 == 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 ==
-[[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 18: / Line 17: @@
    <jmolCheckbox>
      <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z6/2z64_consurf.spt"</scriptWhenChecked>
-     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
    </jmolCheckbox>
@@ Line 40: / Line 39: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Kim, H M]]
+[[Category: Kim HM]]
-[[Category: Lee, J O]]
+[[Category: Lee J-O]]
-[[Category: Park, B S]]
+[[Category: Park BS]]
-[[Category: Disease mutation]]
-[[Category: Glycoprotein]]
-[[Category: Immune response]]
-[[Category: Immune system]]
-[[Category: Inflammatory response]]
-[[Category: Innate immunity]]
-[[Category: Leucine-rich repeat]]
-[[Category: Lp]]
-[[Category: Md-2]]
-[[Category: Membrane]]
-[[Category: Secreted]]
-[[Category: Tlr4]]
-[[Category: Toll-like receptor]]
-[[Category: Transmembrane]]

2z64: Difference between revisions

Latest revision as of 08:08, 23 October 2024

Crystal structure of mouse TLR4 and mouse MD-2 complex

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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