2z7x

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(New page: 200px<br /><applet load="2z7x" size="350" color="white" frame="true" align="right" spinBox="true" caption="2z7x, resolution 2.10&Aring;" /> '''Crystal structure of...)
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[[Image:2z7x.gif|left|200px]]<br /><applet load="2z7x" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2z7x, resolution 2.10&Aring;" />
 
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'''Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide'''<br />
 
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==Overview==
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==Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide==
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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.
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<StructureSection load='2z7x' size='340' side='right'caption='[[2z7x]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2z7x]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Eptatretus_burgeri Eptatretus burgeri], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. 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=2Z7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z7X FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=PCJ:(2R)-3-{[(2S)-3-HYDROXY-2-(PALMITOYLAMINO)PROPYL]THIO}PROPANE-1,2-DIYL+DIHEXADECANOATE'>PCJ</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2z7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z7x OCA], [https://pdbe.org/2z7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2z7x RCSB], [https://www.ebi.ac.uk/pdbsum/2z7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2z7x ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z7/2z7x_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2z7x ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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2Z7X is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens,_eptatretus_burgeri Homo sapiens, eptatretus burgeri] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=NDG:'>NDG</scene> and <scene name='pdbligand=PCJ:'>PCJ</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z7X OCA].
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*[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]]
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*[[Variable lymphocyte receptor 3D structures|Variable lymphocyte receptor 3D structures]]
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==Reference==
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__TOC__
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17889651 17889651]
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</StructureSection>
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[[Category: Homo sapiens, eptatretus burgeri]]
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[[Category: Eptatretus burgeri]]
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[[Category: Protein complex]]
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[[Category: Homo sapiens]]
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[[Category: Heo, J.Y.]]
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[[Category: Large Structures]]
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[[Category: Jin, M.S.]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Kim, S.E.]]
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[[Category: Synthetic construct]]
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[[Category: Lee, J.O.]]
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[[Category: Toll-like Receptors]]
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[[Category: NAG]]
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[[Category: Heo JY]]
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[[Category: NDG]]
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[[Category: Jin MS]]
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[[Category: PCJ]]
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[[Category: Kim SE]]
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[[Category: cytoplasmic vesicle]]
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[[Category: Lee JO]]
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[[Category: glycoprotein]]
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[[Category: immune response]]
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[[Category: immune system]]
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[[Category: inflammatory response]]
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[[Category: innate immunity]]
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[[Category: leucine-rich repeat]]
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[[Category: lipopeptide]]
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[[Category: membrane]]
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[[Category: pam3csk4]]
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[[Category: polymorphism]]
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[[Category: receptor]]
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[[Category: tlr1]]
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[[Category: tlr2]]
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[[Category: transmembrane]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:51:47 2008''
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Current revision

Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide

PDB ID 2z7x

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