Bone morphogenic proteins (BMPs) are homodimeric molecules (MW 25-30 Kd) that regulate various cellular functions such as bone induction, morphogenesis, chemotaxis, mitosis, hematopoiesis, cell survival, and apoptosis. The osteogenic properties of BMPs led to their discovery in demineralized bone extracts1 and explained why bone is capable of rapid regeneration. BMPs also act on tissues such as eye, testis, kidney, neurons, teeth, and heart.
About fourteen BMPs have been isolated and cloned from the extracellular matrix. BMPs are members of the TGF-beta Superfamily, with the exception of BMP-1, which is a protease that processes the carboxy-terminal pro-collagen peptide.2 Although the sequences of members of the TGF-beta Superfamily vary considerably, all are structurally very similar. For example, TGF-beta 2 and BMP-7 each have a cysteine knot formed by three internal disulfide bridges between highly conserved cysteine residues in each subunit.3 A fourth intermolecular disulfide bond stabilizes the dimer. Solvent accessible loops, where the primary structure shows higher diversity, from both subunits of the dimer are brought together in the folded molecule and form a ridge that is thought to form the receptor-binding site.
BMPs bind specifically to type I and type II serine/threonine kinase receptors with dissociation constants in the low nM range.4,5 Binding is tighter in the presence of both receptors.6 Formation of a heteromeric complex between members of the TGF-beta Superfamily and their respective receptors is one of the early events of signal transduction.