title: Identification of a core domain within the proregion of bone morphogenetic proteins that interacts with the dimeric, mature domain.
abstract: Proregions of bone morphogenetic proteins (BMPs) fulfill important biological functions as intramolecular chaperones and for extracellular targeting of the mature signal ligand. Knowledge of the structures of the proregions would contribute to a more comprehensive picture of the biological activities of the pro-forms of BMP growth factors. In this study, a protease resistant core domain of the proregions of three BMPs was identified. For a more detailed analysis, the core domain of the BMP-2 proregion was recombinantly produced. Unfolding/refolding experiments and spectroscopic analyses proved that the core domain can be obtained as a folded entity. Binding of the core domain to the mature growth factor was demonstrated by SPR. Via peptide microarray analysis, residues within the core fragment could be identified that engage in binding to the dimeric, mature domain. Our study reveals that diverse members of the BMP family share a common, independently folding core domain within the large proregions peculiar to TGF-β superfamily members that may serve as a scaffold for folding and assembly of the dimeric proprotein complexes.
authors.affiliation: Institute for Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Kuhfahl
authors.forename: Anja
authors.initials: A
authors.lastname: Hauburger
authors.forename: Tino
authors.initials: T
authors.lastname: Thieme
authors.forename: Jay
authors.initials: J
authors.lastname: Groppe
authors.forename: Christian
authors.initials: C
authors.lastname: Ihling
authors.forename: Sladjana
authors.initials: S
authors.lastname: Tomic
authors.forename: Mike
authors.initials: M
authors.lastname: Schutkowski
authors.forename: Andrea
authors.initials: A
authors.lastname: Sinz
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schwarz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000737:chemistry* / Q000235:genetics; D004331:Drosophila melanogaster; D055412:Growth Differentiation Factors / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D058767:Protein Unfolding
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D055412:Growth Differentiation Factors