2z65

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the human TLR4 TV3 hybrid-MD-2-Eritoran complex

Structural highlights

2z65 is a 4 chain structure with sequence from Eptatretus burgeri and Homo sapiens. 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

Function

LY96_HUMAN 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.

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^[1]

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

References

↑ 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:http://dx.doi.org/10.1016/j.cell.2007.08.002

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/2z65"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human TLR4 TV3 hybrid-MD-2-Eritoran complex==
-<StructureSection load='2z65' size='340' side='right' caption='[[2z65]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='2z65' size='340' side='right'caption='[[2z65]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2z65]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Eptatretus_burgeri Eptatretus burgeri] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z65 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Z65 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2z65]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Eptatretus_burgeri Eptatretus burgeri] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z65 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=E55:3-O-DECYL-2-DEOXY-6-O-{2-DEOXY-3-O-[(3R)-3-METHOXYDECYL]-6-O-METHYL-2-[(11Z)-OCTADEC-11-ENOYLAMINO]-4-O-PHOSPHONO-BETA-D-GLUCOPYRANOSYL}-2-[(3-OXOTETRADECANOYL)AMINO]-1-O-PHOSPHONO-ALPHA-D-GLUCOPYRANOSE'>E55</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene><br>
+</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><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2z62|2z62]], [[2z63|2z63]], [[2z64|2z64]], [[2z66|2z66]]</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=E55:3-O-DECYL-2-DEOXY-6-O-{2-DEOXY-3-O-[(3R)-3-METHOXYDECYL]-6-O-METHYL-2-[(11Z)-OCTADEC-11-ENOYLAMINO]-4-O-PHOSPHONO-BETA-D-GLUCOPYRANOSYL}-2-[(3-OXOTETRADECANOYL)AMINO]-1-O-PHOSPHONO-ALPHA-D-GLUCOPYRANOSE'>E55</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLR4, VLRB.61 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7764 Eptatretus burgeri]), MD-2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=2z65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z65 OCA], [https://pdbe.org/2z65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2z65 RCSB], [https://www.ebi.ac.uk/pdbsum/2z65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2z65 ProSAT]</span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2z65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z65 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2z65 RCSB], [http://www.ebi.ac.uk/pdbsum/2z65 PDBsum]</span></td></tr>
+</table>
-<table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/TLR4_HUMAN TLR4_HUMAN]] Genetic variation in TLR4 is associated with age-related macular degeneration type 10 (ARMD10) [MIM:[http://omim.org/entry/611488 611488]]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
 == Function ==
-[[http://www.uniprot.org/uniprot/TLR4_HUMAN TLR4_HUMAN]] 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. Also involved in LPS-independent inflammatory responses triggered by Ni(2+). These responses require non-conserved histidines and are, therefore, species-specific.<ref>PMID:20711192</ref>  [[http://www.uniprot.org/uniprot/LY96_HUMAN LY96_HUMAN]] 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.
+[https://www.uniprot.org/uniprot/LY96_HUMAN LY96_HUMAN] 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.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z6/2z65_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z6/2z65_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>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2z65 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 30: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2z65" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Toll-like Receptors|Toll-like Receptors]]
+*[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]]
-*[[Variable lymphocyte receptor|Variable lymphocyte receptor]]
+*[[Variable lymphocyte receptor 3D structures|Variable lymphocyte receptor 3D structures]]
 == References ==
 <references/>
@@ Line 40: / Line 39: @@
 [[Category: Eptatretus burgeri]]
 [[Category: Homo sapiens]]
-[[Category: Kim, H M.]]
+[[Category: Large Structures]]
-[[Category: Lee, J O.]]
+[[Category: Kim HM]]
-[[Category: Park, B S.]]
+[[Category: Lee J-O]]
-[[Category: E5564]]
+[[Category: Park BS]]
-[[Category: Eritoran]]
-[[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]]

2z65

From Proteopedia

Current revision

Crystal structure of the human TLR4 TV3 hybrid-MD-2-Eritoran complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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