5i05
Crystal structure of human BMP9 at 1.87 A resolution
Structural highlights
FunctionGDF2_HUMAN Potent circulating inhibitor of angiogenesis. Could be involved in bone formation. Signals through the type I activin receptor ACVRL1 but not other Alks.[1] [2] Publication Abstract from PubMedEndoglin (ENG)/CD105 is an essential endothelial cell co-receptor of the transforming growth factor beta (TGF-beta) 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. Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1.,Saito T, Bokhove M, Croci R, Zamora-Caballero S, Han L, Letarte M, de Sanctis D, Jovine L Cell Rep. 2017 May 30;19(9):1917-1928. doi: 10.1016/j.celrep.2017.05.011. PMID:28564608[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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