2q8o
From Proteopedia
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| - | [[Image:2q8o.jpg|left|200px]]<br /><applet load="2q8o" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2q8o, resolution 1.75Å" /> | ||
| - | '''crystal structure of mouse GITR ligand dimer'''<br /> | ||
| - | == | + | ==crystal structure of mouse GITR ligand dimer== |
| + | <StructureSection load='2q8o' size='340' side='right'caption='[[2q8o]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2q8o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q8O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q8O FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</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=2q8o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8o OCA], [https://pdbe.org/2q8o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q8o RCSB], [https://www.ebi.ac.uk/pdbsum/2q8o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8o ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TNF18_MOUSE TNF18_MOUSE] Cytokine that binds to TNFRSF18/AITR/GITR (PubMed:14521928, PubMed:14647196). Regulates T-cell responses (PubMed:14647196). Can function as costimulator and lower the threshold for T-cell activation and T-cell proliferation (PubMed:14608036, PubMed:15128759). Important for interactions between activated T-lymphocytes and endothelial cells. Mediates activation of NF-kappa-B (PubMed:14521928, PubMed:14647196, PubMed:18178614). Triggers increased phosphorylation of STAT1 and up-regulates expression of VCAM1 and ICAM1 (By similarity). Promotes leukocyte adhesion to endothelial cells (PubMed:23892569). Regulates migration of monocytes from the splenic reservoir to sites of inflammation (PubMed:24107315).[UniProtKB:Q9UNG2]<ref>PMID:14521928</ref> <ref>PMID:14608036</ref> <ref>PMID:14647196</ref> <ref>PMID:15128759</ref> <ref>PMID:18178614</ref> <ref>PMID:23892569</ref> <ref>PMID:24107315</ref> | ||
| + | == 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/q8/2q8o_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2q8o ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
Glucocorticoid-induced TNF receptor ligand (GITRL) is a member of the TNF super family (TNFSF). GITRL plays an important role in controlling regulatory T cells. The crystal structure of the mouse GITRL (mGITRL) was determined to 1.8-A resolution. Contrary to the current paradigm that all ligands in the TNFSF are trimeric, mGITRL associates as dimer through a unique C terminus tethering arm. Analytical ultracentrifuge studies revealed that in solution, the recombinant mGITRL exists as monomers at low concentrations and as dimers at high concentrations. Biochemical studies confirmed that the mGITRL dimer is biologically active. Removal of the three terminal residues in the C terminus resulted in enhanced receptor-mediated NF-kappaB activation than by the wild-type receptor complex. However, deletion of the tethering C-terminus arm led to reduced activity. Our studies suggest that the mGITRL may undergo a dynamic population shift among different oligomeric forms via C terminus-mediated conformational changes. We hypothesize that specific oligomeric forms of GITRL may be used as a means to differentially control GITR receptor signaling in diverse cells. | Glucocorticoid-induced TNF receptor ligand (GITRL) is a member of the TNF super family (TNFSF). GITRL plays an important role in controlling regulatory T cells. The crystal structure of the mouse GITRL (mGITRL) was determined to 1.8-A resolution. Contrary to the current paradigm that all ligands in the TNFSF are trimeric, mGITRL associates as dimer through a unique C terminus tethering arm. Analytical ultracentrifuge studies revealed that in solution, the recombinant mGITRL exists as monomers at low concentrations and as dimers at high concentrations. Biochemical studies confirmed that the mGITRL dimer is biologically active. Removal of the three terminal residues in the C terminus resulted in enhanced receptor-mediated NF-kappaB activation than by the wild-type receptor complex. However, deletion of the tethering C-terminus arm led to reduced activity. Our studies suggest that the mGITRL may undergo a dynamic population shift among different oligomeric forms via C terminus-mediated conformational changes. We hypothesize that specific oligomeric forms of GITRL may be used as a means to differentially control GITR receptor signaling in diverse cells. | ||
| - | + | Structural basis for ligand-mediated mouse GITR activation.,Zhou Z, Tone Y, Song X, Furuuchi K, Lear JD, Waldmann H, Tone M, Greene MI, Murali R Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):641-5. Epub 2008 Jan 4. PMID:18178614<ref>PMID:18178614</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2q8o" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Yukiko T]] | ||
| + | [[Category: Zhaocai Z]] | ||
Current revision
crystal structure of mouse GITR ligand dimer
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