PDBsum entry 5i05

Signaling protein

PDB id: 5i05

Contents

Protein chain

107 a.a.

Ligands

GOL ×2

Waters ×52

PDB id:

5i05

Name:

Signaling protein

Title:

Crystal structure of human bmp9 at 1.87 a resolution

Structure:

Growth/differentiation factor 2. Chain: a. Fragment: unp residues 320-429. Synonym: gdf-2,bone morphogenetic protein 9,bmp-9. Engineered: yes. Other_details: mature bmp9

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell: endothelial. Gene: gdf2, bmp9. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293s. Expression_system_atcc_number: crl-3022.

Resolution:

1.87Å R-factor: 0.216 R-free: 0.233

Authors:

T.Saito,M.Bokhove,L.Jovine

Key ref:

T.Saito et al. (2017). Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1. Cell Rep, 19, 1917-1928. PubMed id: 28564608

Date:

03-Feb-16 Release date: 07-Jun-17

Protein chain

Q9UK05  (GDF2_HUMAN) -  Growth/differentiation factor 2 from Homo sapiens

Seq: 429 a.a.

Struc: 107 a.a.

Cell Rep 19:1917-1928 (2017)

PubMed id: 28564608

Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1.

T.Saito, M.Bokhove, R.Croci, S.Zamora-Caballero, L.Han, M.Letarte, D.de Sanctis, L.Jovine.

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.