7KHD

Human GITR-GITRL complex

7KHD の概要

• エントリーDOI: 10.2210/pdb7khd/pdb
• 分子名称: Tumor necrosis factor ligand superfamily member 18, Tumor necrosis factor receptor superfamily member 18, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: tnfrsf, receptor-ligand complex, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 59206.97

構造登録者

Wang, F.,Chau, B.,West, S.M.,Strop, P. (登録日: 2020-10-21, 公開日: 2021-03-03, 最終更新日: 2024-11-13)

主引用文献

Wang, F.,Chau, B.,West, S.M.,Kimberlin, C.R.,Cao, F.,Schwarz, F.,Aguilar, B.,Han, M.,Morishige, W.,Bee, C.,Dollinger, G.,Rajpal, A.,Strop, P.
Structures of mouse and human GITR-GITRL complexes reveal unique TNF superfamily interactions.
Nat Commun, 12:1378-1378, 2021

PubMed Abstract: Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) are members of the tumor necrosis superfamily that play a role in immune cell signaling, activation, and survival. GITR is a therapeutic target for directly activating effector CD4 and CD8 T cells, or depleting GITR-expressing regulatory T cells (Tregs), thereby promoting anti-tumor immune responses. GITR activation through its native ligand is important for understanding immune signaling, but GITR structure has not been reported. Here we present structures of human and mouse GITR receptors bound to their cognate ligands. Both species share a receptor-ligand interface and receptor-receptor interface; the unique C-terminal receptor-receptor enables higher order structures on the membrane. Human GITR-GITRL has potential to form a hexameric network of membrane complexes, while murine GITR-GITRL complex forms a linear chain due to dimeric interactions. Mutations at the receptor-receptor interface in human GITR reduce cell signaling with in vitro ligand binding assays and minimize higher order membrane structures when bound by fluorescently labeled ligand in cell imaging experiments.

PubMed: 33654081
DOI: 10.1038/s41467-021-21563-z

実験手法

X-RAY DIFFRACTION (2.95610193196 Å)