title: Folding and dimerization kinetics of bone morphogenetic protein-2, a member of the transforming growth factor-β family.
abstract: The kinetics of folding and dimerization of bone morphogenetic protein-2 (BMP-2), a disulfide-connected, homodimeric cystine-knot protein and a member of the transforming growth factor-β superfamily, was analyzed under a variety of different conditions. Refolding and dimerization of BMP-2 were extremely slow under all conditions studied, and could be described by consecutive first-order reactions involving at least one long-lived intermediate. The rate constants vary from ~ 0.2 × 10(-5) to ~ 3.5 × 10(-5) s(-1), and were strongly dependent on temperature, redox conditions, and the presence of stabilizing or destabilizing ions. In particular, the combined impact of ionic strength and redox conditions on the rates indicates that electrostatic interactions control thiol-disulfide exchange reactions on the path from the unfolded and reduced monomers to the disulfide-connected growth factor in a rate-determining way.
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Vallejo
authors.forename: Ursula
authors.initials: U
authors.lastname: Rinas
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry*; D002021:Buffers; D019803:Glutathione Disulfide / Q000737:chemistry; D019791:Guanidine / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D010084:Oxidation-Reduction; D011489:Protein Denaturation; D017510:Protein Folding; D055503:Protein Multimerization; D055550:Protein Stability; D012965:Sodium Chloride / Q000737:chemistry; D055411:TGF-beta Superfamily Proteins / Q000737:chemistry
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D002021:Buffers; D055411:TGF-beta Superfamily Proteins; D012965:Sodium Chloride; D019791:Guanidine; D019803:Glutathione Disulfide