4mpl | pdb_00004mpl

Crystal structure of BMP9 at 1.90 Angstrom

spinqualitylabelsall models 4mpl, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mpl is a 1 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 1.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GDF2_HUMAN Potent circulating inhibitor of angiogenesis. Could be involved in bone formation. Signals through the type I activin receptor ACVRL1 but not other Alks. Publication Abstract from PubMed BMP9, a member of the TGFbeta superfamily, is a homodimer that forms a signaling complex with two type I and two type II receptors. Signaling through high-affinity activin receptor-like kinase 1 (ALK1) in endothelial cells, circulating BMP9 acts as a vascular quiescence factor, maintaining endothelial homeostasis. BMP9 is also the most potent BMP for inducing osteogenic signaling in mesenchymal stem cells in vitro and promoting bone formation in vivo. This activity requires ALK1, the lower-affinity type I receptor ALK2, and higher concentrations of BMP9. In adults, BMP9 is constitutively expressed in hepatocytes and secreted into the circulation. Optimum concentrations of BMP9 are essential to maintain the highly specific endothelial-protective function. Factors regulating BMP9 stability and activity remain unknown. Here, we showed by chromatography and a 1.9 A crystal structure that stable BMP9 dimers could form either with (D-form) or without (M-form) an intermolecular disulfide bond. Although both forms of BMP9 were capable of binding to the prodomain and ALK1, the M-form demonstrated less sustained induction of Smad1/5/8 phosphorylation. The two forms could be converted into each other by changing the redox potential and this redox switch caused a major alteration in BMP9 stability. The M-form displayed greater susceptibility to redox-dependent cleavage by proteases present in serum. This study provides a mechanism for the regulation of circulating BMP9 concentrations, and may provide new rationales for approaches to modify BMP9 levels for therapeutic purposes. Regulation of Bone Morphogenetic Protein 9 by Redox-Dependent Proteolysis.,Wei Z, Salmon RM, Upton PD, Morrell NW, Li W J Biol Chem. 2014 Sep 18. pii: jbc.M114.579771. PMID:25237187 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Growth differentiation factor 3D STRUCTURES

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