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2z80
From Proteopedia
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| - | [[Image:2z80.gif|left|200px]] | ||
| - | + | ==Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide== | |
| - | + | <StructureSection load='2z80' size='340' side='right'caption='[[2z80]], [[Resolution|resolution]] 1.80Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | | | + | <table><tr><td colspan='2'>[[2z80]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z80 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z80 FirstGlance]. <br> |
| - | | | + | </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></td></tr> |
| - | | | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2z7x|2z7x]], [[2z81|2z81]], [[2z82|2z82]]</div></td></tr> |
| - | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLR2, TIL4, VLRB ([https://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=2z80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z80 OCA], [https://pdbe.org/2z80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2z80 RCSB], [https://www.ebi.ac.uk/pdbsum/2z80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2z80 ProSAT]</span></td></tr> | |
| - | ''' | + | </table> |
| - | + | == Function == | |
| - | + | [[https://www.uniprot.org/uniprot/TLR2_HUMAN TLR2_HUMAN]] Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. May also promote apoptosis in response to lipoproteins. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR6. | |
| - | == | + | == 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/z8/2z80_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/main_output.php?pdb_ID=2z80 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
TLR2 in association with TLR1 or TLR6 plays an important role in the innate immune response by recognizing microbial lipoproteins and lipopeptides. Here we present the crystal structures of the human TLR1-TLR2-lipopeptide complex and of the mouse TLR2-lipopeptide complex. Binding of the tri-acylated lipopeptide, Pam(3)CSK(4), induced the formation of an "m" shaped heterodimer of the TLR1 and TLR2 ectodomains whereas binding of the di-acylated lipopeptide, Pam(2)CSK(4), did not. The three lipid chains of Pam(3)CSK(4) mediate the heterodimerization of the receptor; the two ester-bound lipid chains are inserted into a pocket in TLR2, while the amide-bound lipid chain is inserted into a hydrophobic channel in TLR1. An extensive hydrogen-bonding network, as well as hydrophobic interactions, between TLR1 and TLR2 further stabilize the heterodimer. We propose that formation of the TLR1-TLR2 heterodimer brings the intracellular TIR domains close to each other to promote dimerization and initiate signaling. | TLR2 in association with TLR1 or TLR6 plays an important role in the innate immune response by recognizing microbial lipoproteins and lipopeptides. Here we present the crystal structures of the human TLR1-TLR2-lipopeptide complex and of the mouse TLR2-lipopeptide complex. Binding of the tri-acylated lipopeptide, Pam(3)CSK(4), induced the formation of an "m" shaped heterodimer of the TLR1 and TLR2 ectodomains whereas binding of the di-acylated lipopeptide, Pam(2)CSK(4), did not. The three lipid chains of Pam(3)CSK(4) mediate the heterodimerization of the receptor; the two ester-bound lipid chains are inserted into a pocket in TLR2, while the amide-bound lipid chain is inserted into a hydrophobic channel in TLR1. An extensive hydrogen-bonding network, as well as hydrophobic interactions, between TLR1 and TLR2 further stabilize the heterodimer. We propose that formation of the TLR1-TLR2 heterodimer brings the intracellular TIR domains close to each other to promote dimerization and initiate signaling. | ||
| - | + | Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide.,Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, Lee H, Lee JO Cell. 2007 Sep 21;130(6):1071-82. PMID:17889651<ref>PMID:17889651</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2z80" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]] | ||
| + | *[[Variable lymphocyte receptor 3D structures|Variable lymphocyte receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Heo, J Y]] | ||
| + | [[Category: Jin, M S]] | ||
| + | [[Category: Kim, S E]] | ||
| + | [[Category: Lee, J O]] | ||
| + | [[Category: Glycoprotein]] | ||
| + | [[Category: Immune response]] | ||
| + | [[Category: Immune system]] | ||
| + | [[Category: Inflammatory response]] | ||
| + | [[Category: Innate immunity]] | ||
| + | [[Category: Leucine-rich repeat]] | ||
| + | [[Category: Lipopeptide]] | ||
| + | [[Category: Membrane]] | ||
| + | [[Category: Receptor]] | ||
| + | [[Category: Tlr2]] | ||
| + | [[Category: Transmembrane]] | ||
Current revision
Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide
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