8ZUJ

Pentagonal cluster of BAFF-BAFFR ectodomain complex

8ZUJ の概要

• エントリーDOI: 10.2210/pdb8zuj/pdb
• 関連するPDBエントリー: 8ZUI 8ZUK
• EMDBエントリー: 60485
• 分子名称: Tumor necrosis factor receptor superfamily member 13C, Tumor necrosis factor ligand superfamily member 13b, soluble form (2 entities in total)
• 機能のキーワード: baff receptor, receptor, receptor cluster, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 30
• 化学式量合計: 419814.56

構造登録者

Lim, C.S.,Lee, J.O. (登録日: 2024-06-09, 公開日: 2025-06-11, 最終更新日: 2025-08-06)

主引用文献

Lim, C.S.,Lee, J.,Kim, J.W.,Lee, J.O.
Highly ordered clustering of TNF alpha and BAFF ligand-receptor-intracellular adaptor complexes on a lipid membrane.
Nat Commun, 16:5551-5551, 2025

PubMed Abstract: The TNF family plays a critical role in immune regulation. Here, we present high-resolution structures of clusters formed by two TNF receptor family proteins, TNFR1 and BAFFR. Using a lipid monolayer method to mimic their membrane-bound state, we observe that the TNFα-TNFR1 complex forms highly ordered clusters of trimers on the lipid membrane. A non-competitive TNFR1 antagonist that inhibits receptor activation disrupted these clusters without blocking ligand binding or receptor trimerization. Furthermore, we find that the BAFF-BAFFR, BAFF-TACI, and BAFF-BCMA receptor-ligand complexes predominantly form pentagonal clusters of trimers on the lipid membrane. Notably, the binding of the intracellular adaptor TRAF3 to the BAFF-BAFFR complex induces a structural transition from a pentagonal to a flat hexagonal cluster. Mutations in BAFF that impair BAFFR activation prevented cluster formation. Our findings demonstrate that ligand binding induces the formation of highly ordered clusters of TNFR1 and BAFFR receptors on the lipid membrane, which is essential for their activation.

PubMed: 40593711
DOI: 10.1038/s41467-025-61271-6

実験手法

ELECTRON MICROSCOPY (2.58 Å)