7X9G

Crystal structure of human EDA and EDAR

7X9G の概要

• エントリーDOI: 10.2210/pdb7x9g/pdb
• 分子名称: Ectodysplasin-A, secreted form, Tumor necrosis factor receptor superfamily member EDAR (2 entities in total)
• 機能のキーワード: ligand-receptor complex, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 48586.94

構造登録者

Yu, K.,Wan, F.,Huang, C.,Wu, J.,Lei, M. (登録日: 2022-03-15, 公開日: 2023-02-22, 最終更新日: 2024-11-20)

主引用文献

Yu, K.,Huang, C.,Wan, F.,Jiang, C.,Chen, J.,Li, X.,Wang, F.,Wu, J.,Lei, M.,Wu, Y.
Structural insights into pathogenic mechanism of hypohidrotic ectodermal dysplasia caused by ectodysplasin A variants.
Nat Commun, 14:767-767, 2023

PubMed Abstract: EDA is a tumor necrosis factor (TNF) family member, which functions together with its cognate receptor EDAR during ectodermal organ development. Mutations of EDA have long been known to cause X-linked hypohidrotic dysplasia in humans characterized by primary defects in teeth, hair and sweat glands. However, the structural information of EDA interaction with EDAR is lacking and the pathogenic mechanism of EDA variants is poorly understood. Here, we report the crystal structure of EDA C-terminal TNF homology domain bound to the N-terminal cysteine-rich domains of EDAR. Together with biochemical, cellular and mouse genetic studies, we show that different EDA mutations lead to varying degrees of ectodermal developmental defects in mice, which is consistent with the clinical observations on human patients. Our work extends the understanding of the EDA signaling mechanism, and provides important insights into the molecular pathogenesis of disease-causing EDA variants.

PubMed: 36765055
DOI: 10.1038/s41467-023-36367-6

実験手法

X-RAY DIFFRACTION (2.8 Å)