1ZKZ

Crystal Structure of BMP9

Summary for 1ZKZ

• Entry DOI: 10.2210/pdb1zkz/pdb
• Descriptor: Growth/differentiation factor 2 (2 entities in total)
• Functional Keywords: glycoprotein, growth factor, cytokine, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted : Q9UK05
• Total number of polymer chains: 1
• Total formula weight: 12102.97

Authors

Brown, M.A.,Zhao, Q.,Baker, K.A.,Naik, C.,Chen, C.,Pukac, L.,Singh, M.,Tsareva, T.,Parice, Y.,Mahoney, A.,Roschke, V.,Sanyal, I.,Choe, S. (deposition date: 2005-05-04, release date: 2005-05-24, Last modification date: 2024-11-06)

Primary citation

Brown, M.A.,Zhao, Q.,Baker, K.A.,Naik, C.,Chen, C.,Pukac, L.,Singh, M.,Tsareva, T.,Parice, Y.,Mahoney, A.,Roschke, V.,Sanyal, I.,Choe, S.
Crystal structure of BMP-9 and functional interactions with pro-region and receptors
J.Biol.Chem., 280:25111-25118, 2005

PubMed Abstract: Bone morphogenetic proteins (BMPs), a subset of the transforming growth factor (TGF)-beta superfamily, regulate a diverse array of cellular functions during development and in the adult. BMP-9 (also known as growth and differentiation factor (GDF)-2) potently induces osteogenesis and chondrogenesis, has been implicated in the differentiation of cholinergic neurons, and may help regulate glucose metabolism. We have determined the structure of BMP-9 to 2.3 A and examined the differences between our model and existing crystal structures of other BMPs, both in isolation and in complex with their receptors. TGF-beta ligands are translated as precursors, with pro-regions that generally dissociate after cleavage from the ligand, but in some cases (including GDF-8 and TGF-beta1, -2, and -3), the pro-region remains associated after secretion from the cell and inhibits binding of the ligand to its receptor. Although the proregion of BMP-9 remains tightly associated after secretion, we find, in several cell-based assays, that the activities of BMP-9 and BMP-9.pro-region complex were equivalent. Activin receptor-like kinase 1 (ALK-1), an orphan receptor in the TGF-beta family, was also identified as a potential receptor for BMP-9 based on surface plasmon resonance studies (BIAcore) and the ability of soluble ALK-1 to block the activity of BMP-9.pro-region complex in cell-based assays.

PubMed: 15851468
DOI: 10.1074/jbc.M503328200

Experimental method

X-RAY DIFFRACTION (2.33 Å)