5I04

Crystal structure of the orphan region of human endoglin/CD105

5I04 の概要

• エントリーDOI: 10.2210/pdb5i04/pdb
• 関連するPDBエントリー: 5HZV 5HZW 5I05
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: Maltose-binding periplasmic protein,Endoglin, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: orphan domain, angiogenesis, glycoprotein, receptor, signaling protein
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 76268.36

構造登録者

Saito, T.,Bokhove, M.,de Sanctis, D.,Jovine, L. (登録日: 2016-02-03, 公開日: 2017-06-07, 最終更新日: 2024-10-16)

主引用文献

Saito, T.,Bokhove, M.,Croci, R.,Zamora-Caballero, S.,Han, L.,Letarte, M.,de Sanctis, D.,Jovine, L.
Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1.
Cell Rep, 19:1917-1928, 2017

PubMed Abstract: Endoglin (ENG)/CD105 is an essential endothelial cell co-receptor of the transforming growth factor β (TGF-β) superfamily, mutated in hereditary hemorrhagic telangiectasia type 1 (HHT1) and involved in tumor angiogenesis and preeclampsia. Here, we present crystal structures of the ectodomain of human ENG and its complex with the ligand bone morphogenetic protein 9 (BMP9). BMP9 interacts with a hydrophobic surface of the N-terminal orphan domain of ENG, which adopts a new duplicated fold generated by circular permutation. The interface involves residues mutated in HHT1 and overlaps with the epitope of tumor-suppressing anti-ENG monoclonal TRC105. The structure of the C-terminal zona pellucida module suggests how two copies of ENG embrace homodimeric BMP9, whose binding is compatible with ligand recognition by type I but not type II receptors. These findings shed light on the molecular basis of the BMP signaling cascade, with implications for future therapeutic interventions in this fundamental pathway.

PubMed: 28564608
DOI: 10.1016/j.celrep.2017.05.011

実験手法

X-RAY DIFFRACTION (2.42 Å)