6A3V

Complex structure of human 4-1BB and 4-1BBL

6A3V の概要

• エントリーDOI: 10.2210/pdb6a3v/pdb
• 分子名称: Tumor necrosis factor ligand superfamily member 9, Tumor necrosis factor receptor superfamily member 9, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: complex structure, agonist monoclonal antibody, cross-linking, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 24
• 化学式量合計: 471146.77

構造登録者

Li, Y.,Zhang, C.,Chai, Y.,Qi, J.,Tien, P.,Gao, S.,Gao, G.F. (登録日: 2018-06-17, 公開日: 2018-10-10, 最終更新日: 2024-10-23)

主引用文献

Li, Y.,Tan, S.,Zhang, C.,Chai, Y.,He, M.,Zhang, C.W.,Wang, Q.,Tong, Z.,Liu, K.,Lei, Y.,Liu, W.J.,Liu, Y.,Tian, Z.,Cao, X.,Yan, J.,Qi, J.,Tien, P.,Gao, S.,Gao, G.F.
Limited Cross-Linking of 4-1BB by 4-1BB Ligand and the Agonist Monoclonal Antibody Utomilumab.
Cell Rep, 25:909-920.e4, 2018

PubMed Abstract: Monoclonal antibodies (mAbs) targeting the co-stimulatory molecule 4-1BB are of interest for tumor immunotherapy. We determined the complex structures of human 4-1BB with 4-1BB ligand (4-1BBL) or utomilumab to elucidate the structural basis of 4-1BB activation. The 4-1BB/4-1BBL complex displays a typical TNF/TNFR family binding mode. The structure of utomilumab/4-1BB complex shows that utomilumab binds to dimeric 4-1BB with a distinct but partially overlapping binding area with 4-1BBL. Competitive binding analysis demonstrates that utomilumab blocks the 4-1BB/4-1BBL interaction, indicating the interruption of ligand-mediated signaling. The binding profiles of 4-1BBL and utomilumab to monomeric or dimeric 4-1BB indicate limited cross-linking of 4-1BB molecules. These findings provide mechanistic insight into the binding of 4-1BB with its ligand and its agonist mAb, which may facilitate the future development of anti-4-1BB biologics for tumor immunotherapy.

PubMed: 30355497
DOI: 10.1016/j.celrep.2018.09.073

実験手法

X-RAY DIFFRACTION (3.391 Å)