Molecular Basis of Interchain Disulfide Bond Formation in BMP-9 and BMP-10.

ABSTRACT: BMP-9 and BMP-10 are TGF-β family signaling ligands naturally secreted into blood. They act on endothelial cells and are required for proper development and maintenance of the vasculature. In hereditary hemorrhagic telangiectasia, regulation is disrupted due to mutations in the BMP-9/10 pathway, namely in the type I receptor ALK1 or the co-receptor endoglin. It has been demonstrated that BMP-9/10 heterodimers are the most abundant signaling species in the blood, but it is unclear how they form. Unlike other ligands of the TGF-β family, BMP-9 and -10 are secreted as a mixture of disulfide-linked dimers and monomers, in which the interchain cysteine (Cys-392) remains either paired or unpaired. Here, we show that the monomers are secreted in a cysteinylated form that crystallizes as a non-cov

SUBMITTER: Schwartze TA 

PROVIDER: S-EPMC12148503 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature