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==Crystal structure of the human TLR4-human MD-2-E.coli LPS Ra complex==
==Crystal structure of the human TLR4-human MD-2-E.coli LPS Ra complex==
<StructureSection load='3fxi' size='340' side='right' caption='[[3fxi]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
<StructureSection load='3fxi' size='340' side='right'caption='[[3fxi]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3fxi]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. The November 2011 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Toll-like Receptors''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2011_11 10.2210/rcsb_pdb/mom_2011_11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FXI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FXI FirstGlance]. <br>
<table><tr><td colspan='2'>[[3fxi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The November 2011 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Toll-like Receptors''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2011_11 10.2210/rcsb_pdb/mom_2011_11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FXI 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=FTT:3-HYDROXY-TETRADECANOIC+ACID'>FTT</scene>, <scene name='pdbligand=GCS:D-GLUCOSAMINE'>GCS</scene>, <scene name='pdbligand=GMH:L-GLYCERO-D-MANNO-HEPTOPYRANOSE'>GMH</scene>, <scene name='pdbligand=KDO:3-DEOXY-D-MANNO-OCT-2-ULOSONIC+ACID'>KDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PA1:2-AMINO-2-DEOXY-ALPHA-D-GLUCOPYRANOSE'>PA1</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 3.1&#8491;</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=9606 HUMAN]), ESOP1, LY96, MD-2, MD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=FTT:3-HYDROXY-TETRADECANOIC+ACID'>FTT</scene>, <scene name='pdbligand=GCS:D-GLUCOSAMINE'>GCS</scene>, <scene name='pdbligand=GMH:L-GLYCERO-D-MANNO-HEPTOPYRANOSE'>GMH</scene>, <scene name='pdbligand=KDO:3-DEOXY-D-MANNO-OCT-2-ULOSONIC+ACID'>KDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PA1:2-AMINO-2-DEOXY-ALPHA-D-GLUCOPYRANOSE'>PA1</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=3fxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fxi OCA], [http://pdbe.org/3fxi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fxi RCSB], [http://www.ebi.ac.uk/pdbsum/3fxi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fxi 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=3fxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fxi OCA], [https://pdbe.org/3fxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fxi RCSB], [https://www.ebi.ac.uk/pdbsum/3fxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fxi ProSAT]</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 ==
== 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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fx/3fxi_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fx/3fxi_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>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
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==See Also==
==See Also==
*[[Toll-like Receptors|Toll-like Receptors]]
*[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Toll-like Receptors]]
[[Category: Toll-like Receptors]]
[[Category: Kim, H M]]
[[Category: Kim HM]]
[[Category: Lee, J O]]
[[Category: Lee J-O]]
[[Category: Park, B S]]
[[Category: Park BS]]
[[Category: Song, D H]]
[[Category: Song DH]]
[[Category: Glycoprotein]]
[[Category: Immune response]]
[[Category: Immune system]]
[[Category: Inflammatory response]]
[[Category: Innate immunity]]
[[Category: Leucine rich repeat]]
[[Category: Membrane]]
[[Category: Receptor]]
[[Category: Secreted]]
[[Category: Transmembrane]]

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