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| | ==Crystal Structure of mouse GITRL at 2.5 A.== | | ==Crystal Structure of mouse GITRL at 2.5 A.== |
| - | <StructureSection load='3b9i' size='340' side='right' caption='[[3b9i]], [[Resolution|resolution]] 2.49Å' scene=''> | + | <StructureSection load='3b9i' size='340' side='right'caption='[[3b9i]], [[Resolution|resolution]] 2.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3b9i]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B9I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3B9I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3b9i]] 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=3B9I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3B9I FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qdn|2qdn]]</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]] 2.49Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tnfsf18, Gitrl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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=3b9i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b9i OCA], [https://pdbe.org/3b9i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3b9i RCSB], [https://www.ebi.ac.uk/pdbsum/3b9i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3b9i 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=3b9i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b9i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3b9i RCSB], [http://www.ebi.ac.uk/pdbsum/3b9i PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q7TS55_MOUSE Q7TS55_MOUSE]] Cytokine that binds to TNFRSF18/AITR/GITR. Regulates T-cell responses. Can function as costimulator and lower the threshold for T-cell activation and T-cell proliferation. Important for interactions between activated T-lymphocytes and endothelial cells. Mediates activation of NF-kappa-B.<ref>PMID:14521928</ref> <ref>PMID:14647196</ref> <ref>PMID:14608036</ref> <ref>PMID:15128759</ref> <ref>PMID:18178614</ref> | + | [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 == | | == 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/b9/3b9i_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b9/3b9i_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </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=3b9i ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3b9i" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]] | + | *[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]] |
| | + | *[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Almo, S C]] | + | [[Category: Almo SC]] |
| - | [[Category: Chattopadhyay, K]] | + | [[Category: Chattopadhyay K]] |
| - | [[Category: Nathenson, S G]] | + | [[Category: Nathenson SG]] |
| - | [[Category: Ramagopal, U A]] | + | [[Category: Ramagopal UA]] |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Gitrl]]
| + | |
| - | [[Category: Glucocorticoid-induced tnf receptor ligand]]
| + | |
| - | [[Category: Unknown function]]
| + | |
| Structural highlights
Function
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][1] [2] [3] [4] [5] [6] [7]
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
Glucocorticoid-induced TNF receptor ligand (GITRL), a recently identified member of the TNF superfamily, binds to its receptor, GITR, on both effector and regulatory T cells and generates positive costimulatory signals implicated in a wide range of T cell functions. In contrast to all previously characterized homotrimeric TNF family members, the mouse GITRL crystal structure reveals a previously unrecognized dimeric assembly that is stabilized via a unique "domain-swapping" interaction. Consistent with its crystal structure, mouse GITRL exists as a stable dimer in solution. Structure-guided mutagenesis studies confirmed the determinants responsible for dimerization and support a previously unrecognized receptor-recognition surface for mouse GITRL that has not been observed for any other TNF family members. Taken together, the unique structural and biochemical behavior of mouse GITRL, along with the unusual domain organization of murine GITR, support a previously unrecognized mechanism for signaling within the TNF superfamily.
Evolution of GITRL immune function: murine GITRL exhibits unique structural and biochemical properties within the TNF superfamily.,Chattopadhyay K, Ramagopal UA, Brenowitz M, Nathenson SG, Almo SC Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):635-40. Epub 2008 Jan 8. PMID:18182486[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yu KY, Kim HS, Song SY, Min SS, Jeong JJ, Youn BS. Identification of a ligand for glucocorticoid-induced tumor necrosis factor receptor constitutively expressed in dendritic cells. Biochem Biophys Res Commun. 2003 Oct 17;310(2):433-8. PMID:14521928
- ↑ Tone M, Tone Y, Adams E, Yates SF, Frewin MR, Cobbold SP, Waldmann H. Mouse glucocorticoid-induced tumor necrosis factor receptor ligand is costimulatory for T cells. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15059-64. Epub 2003 Nov 7. PMID:14608036 doi:http://dx.doi.org/10.1073/pnas.2334901100
- ↑ Kim JD, Choi BK, Bae JS, Lee UH, Han IS, Lee HW, Youn BS, Vinay DS, Kwon BS. Cloning and characterization of GITR ligand. Genes Immun. 2003 Dec;4(8):564-9. PMID:14647196 doi:http://dx.doi.org/10.1038/sj.gene.6364026
- ↑ Ji HB, Liao G, Faubion WA, Abadia-Molina AC, Cozzo C, Laroux FS, Caton A, Terhorst C. Cutting edge: the natural ligand for glucocorticoid-induced TNF receptor-related protein abrogates regulatory T cell suppression. J Immunol. 2004 May 15;172(10):5823-7. PMID:15128759
- ↑ Zhou Z, Tone Y, Song X, Furuuchi K, Lear JD, Waldmann H, Tone M, Greene MI, Murali R. Structural basis for ligand-mediated mouse GITR activation. Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):641-5. Epub 2008 Jan 4. PMID:18178614
- ↑ Lacal PM, Petrillo MG, Ruffini F, Muzi A, Bianchini R, Ronchetti S, Migliorati G, Riccardi C, Graziani G, Nocentini G. Glucocorticoid-induced tumor necrosis factor receptor family-related ligand triggering upregulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and promotes leukocyte adhesion. J Pharmacol Exp Ther. 2013 Oct;347(1):164-72. doi: 10.1124/jpet.113.207605. Epub , 2013 Jul 26. PMID:23892569 doi:http://dx.doi.org/10.1124/jpet.113.207605
- ↑ Liao G, van Driel B, Magelky E, O'Keeffe MS, de Waal Malefyt R, Engel P, Herzog RW, Mizoguchi E, Bhan AK, Terhorst C. Glucocorticoid-induced TNF receptor family-related protein ligand regulates the migration of monocytes to the inflamed intestine. FASEB J. 2014 Jan;28(1):474-84. doi: 10.1096/fj.13-236505. Epub 2013 Oct 9. PMID:24107315 doi:http://dx.doi.org/10.1096/fj.13-236505
- ↑ Chattopadhyay K, Ramagopal UA, Brenowitz M, Nathenson SG, Almo SC. Evolution of GITRL immune function: murine GITRL exhibits unique structural and biochemical properties within the TNF superfamily. Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):635-40. Epub 2008 Jan 8. PMID:18182486
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