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3b9i

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Revision as of 07:32, 5 August 2016

Crystal Structure of mouse GITRL at 2.5 A.

Structural highlights

3b9i 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.
Related:	2qdn
Gene:	Tnfsf18, Gitrl (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), 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.

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

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/3b9i"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of mouse GITRL at 2.5 A.==
 <StructureSection load='3b9i' size='340' side='right' caption='[[3b9i]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
 == 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 [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=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>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qdn|2qdn]]</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='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 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=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>
+<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://pdbe.org/3b9i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3b9i RCSB], [http://www.ebi.ac.uk/pdbsum/3b9i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3b9i ProSAT]</span></td></tr>
 </table>
 == 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>
+[[http://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]]
@@ Line 17: / Line 18: @@
     <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=3b9i ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 27: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3b9i" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 34: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Mus musculus]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Almo, S C]]
 [[Category: Chattopadhyay, K]]

3b9i

From Proteopedia

Revision as of 07:32, 5 August 2016

Crystal Structure of mouse GITRL at 2.5 A.

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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