| Structural highlights
Function
[Q80YG2_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.[1] [2] [3] [4] [5]
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[6]
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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
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