9fk5
From Proteopedia
Zebrafish Betaglycan Orphan Domain (zfBGo) in complex with TGF-B3 and extracellular domains of TGFBRI and TGFBRII
Structural highlights
DiseaseTGFB3_HUMAN Defects in TGFB3 are a cause of familial arrhythmogenic right ventricular dysplasia type 1 (ARVD1) [MIM:107970; also known as arrhythmogenic right ventricular cardiomyopathy 1 (ARVC1). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall.[1] FunctionTGFB3_HUMAN Involved in embryogenesis and cell differentiation. Publication Abstract from PubMedBetaglycan (BG) is a transmembrane co-receptor of the transforming growth factor-beta (TGF-beta) 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-beta isoforms to their signaling receptors and is additionally required for inhibin A (InhA) activity. Despite its requirement for the functions of TGF-betas and InhA in vivo, structural information explaining BG ligand selectivity and its mechanism of action is lacking. Here, we determine the structure of TGF-beta 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-beta family, endoglin, thus demonstrating remarkable evolutionary adaptation to enable ligand selectivity. Finally, we provide a structural explanation for the hand-off mechanism underlying TGF-beta signal potentiation. Structures of TGF-beta with betaglycan and signaling receptors reveal mechanisms of complex assembly and signaling.,Wieteska L, Taylor AB, Punch E, Coleman JA, Conway IO, Lin YF, Byeon CH, Hinck CS, Krzysiak T, Ishima R, Lopez-Casillas F, Cherepanov P, Bernard DJ, Hill CS, Hinck AP Nat Commun. 2025 Feb 26;16(1):1778. doi: 10.1038/s41467-025-56796-9. PMID:40011426[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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