9B9F

Zebrafish Betaglycan Orphan Domain (zfBGo) in complex with TGF-B3 and extracellular domains of TGFBRI and TGFBRII

9B9F の概要

• エントリーDOI: 10.2210/pdb9b9f/pdb
• 分子名称: Transforming growth factor beta-3, Transforming growth factor beta-3 triple mutant, Transforming growth factor beta receptor type-1, ... (5 entities in total)
• 機能のキーワード: complex, betaglycan, tgfbr3, tgfb, tgfbr1, tgfbr2, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 170898.78

構造登録者

Wieteska, L.,Taylor, A.B.,Hinck, A.P. (登録日: 2024-04-02, 公開日: 2025-03-12)

主引用文献

Wieteska, L.,Taylor, A.B.,Punch, E.,Coleman, J.A.,Conway, I.O.,Lin, Y.F.,Byeon, C.H.,Hinck, C.S.,Krzysiak, T.,Ishima, R.,Lopez-Casillas, F.,Cherepanov, P.,Bernard, D.J.,Hill, C.S.,Hinck, A.P.
Structures of TGF-beta with betaglycan and signaling receptors reveal mechanisms of complex assembly and signaling.
Nat Commun, 16:1778-1778, 2025

PubMed Abstract: Betaglycan (BG) is a transmembrane co-receptor of the transforming growth factor-β (TGF-β) family of signaling ligands. It is essential for embryonic development, tissue homeostasis and fertility in adults. It functions by enabling binding of the three TGF-β isoforms to their signaling receptors and is additionally required for inhibin A (InhA) activity. Despite its requirement for the functions of TGF-βs and InhA in vivo, structural information explaining BG ligand selectivity and its mechanism of action is lacking. Here, we determine the structure of TGF-β bound both to BG and the signaling receptors, TGFBR1 and TGFBR2. We identify key regions responsible for ligand engagement, which has revealed binding interfaces that differ from those described for the closely related co-receptor of the TGF-β family, endoglin, thus demonstrating remarkable evolutionary adaptation to enable ligand selectivity. Finally, we provide a structural explanation for the hand-off mechanism underlying TGF-β signal potentiation.

PubMed: 40011426
DOI: 10.1038/s41467-025-56796-9

実験手法

X-RAY DIFFRACTION (3 Å)