2R32

Crystal Structure of human GITRL variant

2R32 の概要

• エントリーDOI: 10.2210/pdb2r32/pdb
• 関連するPDBエントリー: 2q1m 2R30
• 分子名称: GCN4-pII/Tumor necrosis factor ligand superfamily member 18 fusion protein, SULFATE ION (3 entities in total)
• 機能のキーワード: gitrl, glucocorticoid-induced tnf receptor ligand, cytokine, glycoprotein, membrane, signal-anchor, transmembrane, immune system
• 由来する生物種: Saccharomyces cerevisiae, Homo sapiens (baker's yeast, human)
• 細胞内の位置: Cell membrane ; Single-pass type II membrane protein : Q9UNG2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19013.78

構造登録者

Chattopadhyay, K.,Ramagopal, U.A.,Nathenson, S.G.,Almo, S.C. (登録日: 2007-08-28, 公開日: 2007-11-20, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.95 Å)