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| | <StructureSection load='5ijc' size='340' side='right'caption='[[5ijc]], [[Resolution|resolution]] 2.57Å' scene=''> | | <StructureSection load='5ijc' size='340' side='right'caption='[[5ijc]], [[Resolution|resolution]] 2.57Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ijc]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bdellostoma_burgeri Bdellostoma burgeri] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5hg4 5hg4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IJC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IJC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ijc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Eptatretus_burgeri Eptatretus burgeri] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5hg4 5hg4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IJC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IJC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=61S:TERT-BUTYL+(2R)-2-({4-AMINO-3-[2-(4-HYDROXYPHENYL)ETHYL]BENZOYL}AMINO)-4-PHENYLBUTANOATE'>61S</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]] 2.57Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ljb|5ljb]], [[5ljd|5ljd]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=V2A:neoseptin+3'>V2A</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VLRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7764 Bdellostoma burgeri]), Ly96, Esop1, Md2 ([http://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=5ijc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ijc OCA], [https://pdbe.org/5ijc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ijc RCSB], [https://www.ebi.ac.uk/pdbsum/5ijc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ijc ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ijc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ijc OCA], [http://pdbe.org/5ijc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ijc RCSB], [http://www.ebi.ac.uk/pdbsum/5ijc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ijc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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 == |
| - | [[http://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> [[http://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/Q4G1L2_EPTBU Q4G1L2_EPTBU] [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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bdellostoma burgeri]] | + | [[Category: Eptatretus burgeri]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Berger, M]] | + | [[Category: Berger M]] |
| - | [[Category: Beutler, B]] | + | [[Category: Beutler B]] |
| - | [[Category: Boger, D L]] | + | [[Category: Boger DL]] |
| - | [[Category: Choi, J H]] | + | [[Category: Choi JH]] |
| - | [[Category: Huang, H]] | + | [[Category: Huang H]] |
| - | [[Category: Jones, B T]] | + | [[Category: Jones BT]] |
| - | [[Category: Moresco, E M]] | + | [[Category: Moresco EM]] |
| - | [[Category: Morin, M D]] | + | [[Category: Morin MD]] |
| - | [[Category: Shi, H]] | + | [[Category: Shi H]] |
| - | [[Category: Su, L]] | + | [[Category: Su L]] |
| - | [[Category: Surakattula, M]] | + | [[Category: Surakattula M]] |
| - | [[Category: Wang, K]] | + | [[Category: Wang K]] |
| - | [[Category: Wang, Y]] | + | [[Category: Wang Y]] |
| - | [[Category: Whitby, L R]] | + | [[Category: Whitby LR]] |
| - | [[Category: Zhan, X]] | + | [[Category: Zhan X]] |
| - | [[Category: Zhang, H]] | + | [[Category: Zhang H]] |
| - | [[Category: Immune response]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Protein complex]]
| + | |
| - | [[Category: Small molecule agonist]]
| + | |
| Structural highlights
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
Q4G1L2_EPTBU 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
Structurally disparate molecules reportedly engage and activate Toll-like receptor (TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by dissimilar ligands remain unknown. We describe Neoseptins, chemically synthesized peptidomimetics that bear no structural similarity to the established TLR4 ligand, lipopolysaccharide (LPS), but productively engage the mouse TLR4 (mTLR4)/myeloid differentiation factor 2 (MD-2) complex. Neoseptin-3 activates mTLR4/MD-2 independently of CD14 and triggers canonical myeloid differentiation primary response gene 88 (MyD88)- and Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)-dependent signaling. The crystal structure mTLR4/MD-2/Neoseptin-3 at 2.57-A resolution reveals that Neoseptin-3 binds as an asymmetrical dimer within the hydrophobic pocket of MD-2, inducing an active receptor complex similar to that induced by lipid A. However, Neoseptin-3 and lipid A form dissimilar molecular contacts to achieve receptor activation; hence strong TLR4/MD-2 agonists need not mimic LPS.
TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS.,Wang Y, Su L, Morin MD, Jones BT, Whitby LR, Surakattula MM, Huang H, Shi H, Choi JH, Wang KW, Moresco EM, Berger M, Zhan X, Zhang H, Boger DL, Beutler B Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):E884-93. doi:, 10.1073/pnas.1525639113. Epub 2016 Feb 1. PMID:26831104[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Wang Y, Su L, Morin MD, Jones BT, Whitby LR, Surakattula MM, Huang H, Shi H, Choi JH, Wang KW, Moresco EM, Berger M, Zhan X, Zhang H, Boger DL, Beutler B. TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS. Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):E884-93. doi:, 10.1073/pnas.1525639113. Epub 2016 Feb 1. PMID:26831104 doi:http://dx.doi.org/10.1073/pnas.1525639113
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