2q8o

From Proteopedia

(Difference between revisions)

Revision as of 08:35, 29 August 2018

crystal structure of mouse GITR ligand dimer

Structural highlights

2q8o is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Tnfsf18 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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) 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^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2q8o"

@@ Line 1: / Line 1: @@
 ==crystal structure of mouse GITR ligand dimer==
 <StructureSection load='2q8o' size='340' side='right' caption='[[2q8o]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2q8o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Q8O FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tnfsf18 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2q8o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8o OCA], [http://pdbe.org/2q8o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2q8o RCSB], [http://www.ebi.ac.uk/pdbsum/2q8o PDBsum]</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=2q8o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8o OCA], [http://pdbe.org/2q8o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2q8o RCSB], [http://www.ebi.ac.uk/pdbsum/2q8o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8o ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 12: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q8/2q8o_consurf.spt"</scriptWhenChecked>
+    <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/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/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=2q8o ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 27: / Line 28: @@
 </div>
 <div class="pdbe-citations 2q8o" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Tumor necrosis factor ligand superfamily|Tumor necrosis factor ligand superfamily]]
 == References ==
 <references/>

2q8o

From Proteopedia

Revision as of 08:35, 29 August 2018

crystal structure of mouse GITR ligand dimer

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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