7x9g

Crystal structure of human EDA and EDAR

spinqualitylabelsall models 7x9g, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7x9g is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease EDA_HUMAN Defects in EDA are the cause of ectodermal dysplasia 1, hypohidrotic, X-linked (XHED) [MIM:305100; also known as Christ-Siemens-Touraine syndrome or X-linked hypohidrotic ectodermal dysplasia (XLHED). Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. XHED is a disease characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands. XHED is the most common form of over 150 clinically distinct ectodermal dysplasias. Defects in EDA are the cause of tooth agenesis selective X-linked type 1 (STHAGX1) [MIM:313500. A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). Function EDA_HUMAN Seems to be involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs. Isoform 1 binds only to the receptor EDAR, while isoform 3 binds exclusively to the receptor XEDAR. Publication Abstract from PubMed 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. Structural insights into pathogenic mechanism of hypohidrotic ectodermal dysplasia caused by ectodysplasin A variants.,Yu K, Huang C, Wan F, Jiang C, Chen J, Li X, Wang F, Wu J, Lei M, Wu Y Nat Commun. 2023 Feb 11;14(1):767. doi: 10.1038/s41467-023-36367-6. PMID:36765055 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tumor necrosis factor receptor 3D structures

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