PDBsum entry: 1zkz

Hormone/growth factor

PDB id: 1zkz

Contents

Protein chain

107 a.a. *

Waters ×40

* Residue conservation analysis

PDB id:

1zkz

Name:

Hormone/growth factor

Title:

Crystal structure of bmp9

Structure:

Growth/differentiation factor 2. Chain: a. Fragment: growth/differentiation factor 2, residues 320-429 synonym: gdf-2, bone morphogenetic protein 9, bmp-9. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: gdf2, bmp9. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_tissue: ovary cells.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.33Å R-factor: 0.233 R-free: 0.272

Authors:

M.A.Brown,Q.Zhao,K.A.Baker,C.Naik,C.Chen,L.Pukac,M.Singh,T.T Y.Parice,A.Mahoney,V.Roschke,I.Sanyal,S.Choe

Key ref:

M.A.Brown et al. (2005). Crystal structure of BMP-9 and functional interactions with pro-region and receptors. J Biol Chem, 280, 25111-25118. PubMed id: 15851468 DOI: 10.1074/jbc.M503328200

Date:

04-May-05 Release date: 24-May-05

Protein chain

Q9UK05  (GDF2_HUMAN) -  Growth/differentiation factor 2

Seq: 429 a.a.

Struc: 107 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (1 term)
• Biochemical function: growth factor activity (1 term)

DOI no: 10.1074/jbc.M503328200

J Biol Chem 280:25111-25118 (2005)

PubMed id: 15851468

Crystal structure of BMP-9 and functional interactions with pro-region and receptors.

M.A.Brown, Q.Zhao, K.A.Baker, C.Naik, C.Chen, L.Pukac, M.Singh, T.Tsareva, Y.Parice, A.Mahoney, V.Roschke, I.Sanyal, S.Choe.

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.

Selected figure(s)

Figure 1.
FIG. 1. Structure of BMP-9. A, Ribbon diagram of BMP-9, showing finger regions 1 and 2 (F1 and F2) and -helix 3 ( 3). The pre-helix loop, which likely encodes specificity determinants, is colored red. C, C terminus; N, N terminus. B, overlay of BMP-9 (blue) and BMP-2 (pink) with BMPR-IA ectodomain. Residues of BMPR-IA within 4.0 Å of BMP-2 are shaded green (36). The carboxyl-terminal residue of BMPR-IA ectodomain is shaded yellow. C, overlay of BMP-9 (blue) and BMP-7 (green) with ActR-II ectodomain. Residues of ActR-II within 4.0 Å of BMP-2 are shaded red (28). The carboxyl-terminal residues of ActR-II ectodomain are shaded yellow. B and C were produced with DINO software (www.dino3d.org).

Figure 2.
FIG. 2. Sequence alignment of BMP-9, BMP-2, BMP-7, BMP-6, and GDF-8. Pro-regions are boxed and shaded gray, furin cleavage sites at the end of each pro-region are boxed in blue. Regions of type II receptor binding are boxed and shaded green (28), regions of type I receptor binding are boxed and shaded purple (27), and conserved cysteines are shaded yellow. Profiles of structural similarity determined by STAMP (34) are boxed in gray. Amino-terminal signal sequences of each protein were omitted from the alignment. Ligands and pro-regions were aligned separately with ClustalW (35).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 25111-25118) copyright 2005.

Figures were selected by an automated process.