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| | ==Crystal structure of the TV8 hybrid of human TLR4 and hagfish VLRB.61== | | ==Crystal structure of the TV8 hybrid of human TLR4 and hagfish VLRB.61== |
| - | <StructureSection load='2z63' size='340' side='right' caption='[[2z63]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='2z63' size='340' side='right'caption='[[2z63]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2z63]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z63 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Z63 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2z63]] is a 1 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=2Z63 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z63 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2z62|2z62]], [[2z64|2z64]], [[2z65|2z65]], [[2z66|2z66]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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, VLRB.61 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2z63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z63 OCA], [https://pdbe.org/2z63 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2z63 RCSB], [https://www.ebi.ac.uk/pdbsum/2z63 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2z63 ProSAT]</span></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=2z63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z63 OCA], [http://pdbe.org/2z63 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2z63 RCSB], [http://www.ebi.ac.uk/pdbsum/2z63 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2z63 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == 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. | + | [https://www.uniprot.org/uniprot/TLR4_HUMAN TLR4_HUMAN] Genetic variation in TLR4 is associated with age-related macular degeneration type 10 (ARMD10) [MIM:[https://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> | + | [https://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> [https://www.uniprot.org/uniprot/Q4G1L2_EPTBU Q4G1L2_EPTBU] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z6/2z63_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z6/2z63_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | ==See Also== | | ==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 == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Eptatretus burgeri]] |
| - | [[Category: Kim, H M]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lee, J O]] | + | [[Category: Large Structures]] |
| - | [[Category: Park, B S]] | + | [[Category: Kim HM]] |
| - | [[Category: Immune system]] | + | [[Category: Lee J-O]] |
| - | [[Category: Lp]]
| + | [[Category: Park BS]] |
| - | [[Category: Md-2]]
| + | |
| - | [[Category: Tlr4]] | + | |
| - | [[Category: Toll-like receptor]]
| + | |
| Structural highlights
Disease
TLR4_HUMAN Genetic variation in TLR4 is associated with age-related macular degeneration type 10 (ARMD10) [MIM: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
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.[1] Q4G1L2_EPTBU
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.
See Also
References
- ↑ Schmidt M, Raghavan B, Muller V, Vogl T, Fejer G, Tchaptchet S, Keck S, Kalis C, Nielsen PJ, Galanos C, Roth J, Skerra A, Martin SF, Freudenberg MA, Goebeler M. Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. Nat Immunol. 2010 Sep;11(9):814-9. doi: 10.1038/ni.1919. Epub 2010 Aug 15. PMID:20711192 doi:10.1038/ni.1919
- ↑ 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
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