Identification of a core domain within the proregion of bone morphogenetic proteins that interacts with the dimeric, mature domain

A core domain of the BMP2 proregion is sufficient for the biogenesis of mature homodimeric growth factor

“…In previous work, protease resistant core domains within the proregions of three BMPs, BMP2, GDF5 and DPP were identified (Kuhfahl et al, 2011). The core domain of the proregion of BMP2 comprising residues 111-241 of prepro-BMP2, has been shown to possess a tertiary fold of moderate stability (ΔG = 11.8 kJ/mol; Table 1) and to bind to the mature part in vitro.…”

“…The core domain of the proregion of BMP2 comprising residues 111-241 of prepro-BMP2, has been shown to possess a tertiary fold of moderate stability (ΔG = 11.8 kJ/mol; Table 1) and to bind to the mature part in vitro. An alignment with the protease Table 1 Biophysical parameters of the 20 kDa core domain, the 15 kDa core domain (Kuhfahl et al, 2011) and the proregion (Hillger et al, 2005). Amino acid positions are based on the sequence of pre-pro-BMP2.…”

“…Flanking DNA sequences belonging to the proregion were looped out in two separate PCR steps (for details see Table S1). Recombinant expression in E. coli cells, inclusion body protein renaturation and subsequent purification was performed as published (Kuhfahl et al, 2011).…”

Cystine knot growth factors and their functionally versatile proregions

“…Limited proteolysis of the proregions and/or pro-forms of BMP2, GDF5 and the Drosophila orthologue of BMP2, decapentaplegic (dpp), led to the identification of protease-resistant sub domains within the proregions (Kuhfahl et al, 2011). These subdomains or core fragments can be independently expressed and show tertiary contacts.…”

The Factor VII-activating Protease (FSAP) Enhances the Activity of Bone Morphogenetic Protein-2 (BMP-2)

“…In the intracellular compartment, the pro-domain regulates the correct folding, dimerization, cleavage, and secretion of the mature BMP (21). Limited proteolysis in combination with a biophysical characterization of a protease-resistant subdomain in the pro-region of pro-BMP-2 revealed a core fragment that might mediate correct folding and dimerization of the growth factor (22). The pro-domain of BMPs can also regulate various aspects of the activity of the mature protein, but this aspect remains largely unexplored (23).…”