5I05

Crystal structure of human BMP9 at 1.87 A resolution

Summary for 5I05

• Entry DOI: 10.2210/pdb5i05/pdb
• Related: 5HZV 5HZW 5I04
• Descriptor: Growth/differentiation factor 2, GLYCEROL (3 entities in total)
• Functional Keywords: growth differentiation factor 2, cell proliferation signal, cytokine, angiogenesis, signaling protein
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted : Q9UK05
• Total number of polymer chains: 1
• Total formula weight: 12287.16

Authors

Saito, T.,Bokhove, M.,Jovine, L. (deposition date: 2016-02-03, release date: 2017-06-07, Last modification date: 2024-10-09)

Primary citation

Saito, T.,Bokhove, M.,Croci, R.,Zamora-Caballero, S.,Han, L.,Letarte, M.,de Sanctis, D.,Jovine, L.
Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1.
Cell Rep, 19:1917-1928, 2017

PubMed Abstract: Endoglin (ENG)/CD105 is an essential endothelial cell co-receptor of the transforming growth factor β (TGF-β) 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.

PubMed: 28564608
DOI: 10.1016/j.celrep.2017.05.011

Experimental method

X-RAY DIFFRACTION (1.87 Å)