6BWV

Crystal Structure of the 4-1BB/4-1BBL Complex

6BWV の概要

• エントリーDOI: 10.2210/pdb6bwv/pdb
• 分子名称: Tumor necrosis factor ligand superfamily member 9, Tumor necrosis factor receptor superfamily member 9, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• 機能のキーワード: tnf superfamily, tnfr superfamily, cd137, 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: 63219.64

構造登録者

Oganesyan, V.,Gilbreth, R.N.,Baca, M. (登録日: 2017-12-15, 公開日: 2018-05-09, 最終更新日: 2024-10-30)

主引用文献

Gilbreth, R.N.,Oganesyan, V.Y.,Amdouni, H.,Novarra, S.,Grinberg, L.,Barnes, A.,Baca, M.
Crystal structure of the human 4-1BB/4-1BBL complex.
J. Biol. Chem., 293:9880-9891, 2018

PubMed Abstract: 4-1BBL is a member of the tumor necrosis factor (TNF) superfamily and is the ligand for the TNFR superfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells, and agonists of this receptor have garnered strong attention as potential immunotherapy agents. Broadly speaking, the structural features of TNF superfamily members, their receptors, and ligand-receptor complexes are similar. However, a published crystal structure of human 4-1BBL suggests that it may be unique in this regard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members. This unusual structure also suggests that the human 4-1BB/4-1BBL complex may be structurally unique within the TNF/TNFR superfamily, but to date no structural data have been reported. Here we report the crystal structure of the human 4-1BB/4-1BBL complex at 2.4-Å resolution. In this structure, 4-1BBL does not adopt the unusual trimer assembly previously reported, but instead forms a canonical bell-shaped trimer typical of other TNF superfamily members. The structure of 4-1BB is also largely canonical as is the 4-1BB/4-1BBL complex. Mutational data support the 4-1BBL structure reported here as being biologically relevant, suggesting that the previously reported structure is not. Together, the data presented here offer insight into structure/function relationships in the 4-1BB/4-1BBL system and improve our structural understanding of the TNF/TNFR superfamily more broadly.

PubMed: 29720399
DOI: 10.1074/jbc.RA118.002803

実験手法

X-RAY DIFFRACTION (2.4 Å)