Structural highlights
Function
TNF18_HUMAN 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]
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 family, 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. Structural analysis reveals that the human GITRL (hGITRL) ectodomain self-assembles into an atypical expanded homotrimer with sparse monomer-monomer interfaces. Consistent with the small intersubunit interfaces, hGITRL exhibits a relatively weak tendency to trimerize in solution and displays a monomer-trimer equilibrium not reported for other TNF family members. This unique assembly behavior has direct implications for hGITRL-GITR signaling, because enforced trimerization of soluble hGITRL ectodomain results in an approximately 100-fold increase in its receptor binding affinity and also in enhanced costimulatory activity. The apparent reduction in affinity that is the consequence of this dynamic equilibrium may represent a mechanism to realize the biologically optimal level of signaling through the hGITRL-GITR pathway, as opposed to the maximal achievable level.
Assembly and structural properties of glucocorticoid-induced TNF receptor ligand: Implications for function.,Chattopadhyay K, Ramagopal UA, Mukhopadhaya A, Malashkevich VN, Dilorenzo TP, Brenowitz M, Nathenson SG, Almo SC Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19452-7. Epub 2007 Nov 26. PMID:18040044[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tuyaerts S, Van Meirvenne S, Bonehill A, Heirman C, Corthals J, Waldmann H, Breckpot K, Thielemans K, Aerts JL. Expression of human GITRL on myeloid dendritic cells enhances their immunostimulatory function but does not abrogate the suppressive effect of CD4+CD25+ regulatory T cells. J Leukoc Biol. 2007 Jul;82(1):93-105. Epub 2007 Apr 20. PMID:17449724 doi:http://dx.doi.org/10.1189/jlb.0906568
- ↑ Chattopadhyay K, Ramagopal UA, Mukhopadhaya A, Malashkevich VN, Dilorenzo TP, Brenowitz M, Nathenson SG, Almo SC. Assembly and structural properties of glucocorticoid-induced TNF receptor ligand: Implications for function. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19452-7. Epub 2007 Nov 26. PMID:18040044
- ↑ Chattopadhyay K, Ramagopal UA, Mukhopadhaya A, Malashkevich VN, Dilorenzo TP, Brenowitz M, Nathenson SG, Almo SC. Assembly and structural properties of glucocorticoid-induced TNF receptor ligand: Implications for function. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19452-7. Epub 2007 Nov 26. PMID:18040044
