7E57

Crystal structure of murine GITR-GITRL complex

7E57 の概要

• エントリーDOI: 10.2210/pdb7e57/pdb
• 分子名称: Tumor necrosis factor ligand superfamily member 18, Tumor necrosis factor receptor superfamily member 18, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: complex, immune system
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 91168.68

構造登録者

Zhao, M.,Tan, S.,Fu, L.,Chai, Y.,Qi, J.,Gao, G.F. (登録日: 2021-02-18, 公開日: 2021-09-29, 最終更新日: 2024-11-13)

主引用文献

Zhao, M.,Fu, L.,Chai, Y.,Sun, M.,Li, Y.,Wang, S.,Qi, J.,Zeng, B.,Kang, L.,Gao, G.F.,Tan, S.
Atypical TNF-TNFR superfamily binding interface in the GITR-GITRL complex for T cell activation.
Cell Rep, 36:109734-109734, 2021

PubMed Abstract: Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is a critical regulatory molecule in modulation of T cell immune responses. Here we report the mouse GITR (mGITR) and mGITR ligand (mGITRL) complex structure and find that the binding interface of mGITR and mGITRL is distinct from the typical tumor necrosis factor superfamily (TNFSF)/TNF receptor superfamily (TNFRSF) members. mGITR binds to its ligand with a single domain, whereas the binding interface on mGITRL is located on the side, which is distal from conserved binding sites of TNFSF molecules. Mutational analysis reveals that the binding interface of GITR/GITRL in humans is conserved with that in the mouse. Substitution of key interacting D93-I94-V95 (DIV) in mGITR with the corresponding K93-F94-S95 (KFS) in human GITR enables cross-recognition with human GITRL and cross-activation of receptor signaling. The findings of this study substantially expand our understanding of the interaction of TNFSF/TNFRSF superfamily molecules and can benefit the future design of biologics by targeting GITR/GITRL.

PubMed: 34551288
DOI: 10.1016/j.celrep.2021.109734

実験手法

X-RAY DIFFRACTION (3.302 Å)