2Q1M

Crystal Structure of human GITRL

Summary for 2Q1M

• Entry DOI: 10.2210/pdb2q1m/pdb
• Descriptor: Tumor necrosis factor ligand superfamily member 18 (2 entities in total)
• Functional Keywords: gitrl; glucocorticoid-induced tnf receptor ligand, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane ; Single-pass type II membrane protein : Q9UNG2
• Total number of polymer chains: 1
• Total formula weight: 14687.74

Authors

Chattopadhyay, K.,Ramagopal, U.A.,Nathenson, S.G.,Almo, S.C. (deposition date: 2007-05-24, release date: 2007-11-13, Last modification date: 2024-10-16)

Primary citation

Chattopadhyay, K.,Ramagopal, U.A.,Mukhopadhaya, A.,Malashkevich, V.N.,Dilorenzo, T.P.,Brenowitz, M.,Nathenson, S.G.,Almo, S.C.
Assembly and structural properties of glucocorticoid-induced TNF receptor ligand: Implications for function.
Proc.Natl.Acad.Sci.USA, 104:19452-19457, 2007

PubMed Abstract: 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.

PubMed: 18040044
DOI: 10.1073/pnas.0709264104

Experimental method

X-RAY DIFFRACTION (2.3 Å)