Folding and dimerization kinetics of bone morphogenetic protein-2, a member of the transforming growth factor-β family.

Vallejo, Luis F; Rinas, Ursula

dc.contributor.author	Vallejo, Luis F
dc.contributor.author	Rinas, Ursula
dc.date.accessioned	2013-04-22T14:40:11Z
dc.date.available	2013-04-22T14:40:11Z
dc.date.issued	2013-01
dc.identifier.citation	Folding and dimerization kinetics of bone morphogenetic protein-2, a member of the transforming growth factor-β family. 2013, 280 (1):83-92 FEBS J.	en_GB
dc.identifier.issn	1742-4658
dc.identifier.pmid	23122408
dc.identifier.doi	10.1111/febs.12051
dc.identifier.uri	http://hdl.handle.net/10033/283572
dc.description.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.
dc.language.iso	en	en
dc.rights	Archived with thanks to The FEBS journal	en_GB
dc.subject.mesh	Bone Morphogenetic Protein 2	en_GB
dc.subject.mesh	Buffers	en_GB
dc.subject.mesh	Glutathione Disulfide	en_GB
dc.subject.mesh	Guanidine	en_GB
dc.subject.mesh	Humans	en_GB
dc.subject.mesh	Kinetics	en_GB
dc.subject.mesh	Models, Biological	en_GB
dc.subject.mesh	Oxidation-Reduction	en_GB
dc.subject.mesh	Protein Denaturation	en_GB
dc.subject.mesh	Protein Folding	en_GB
dc.subject.mesh	Protein Multimerization	en_GB
dc.subject.mesh	Protein Stability	en_GB
dc.subject.mesh	Sodium Chloride	en_GB
dc.subject.mesh	TGF-beta Superfamily Proteins	en_GB
dc.title	Folding and dimerization kinetics of bone morphogenetic protein-2, a member of the transforming growth factor-β family.	en
dc.type	Article	en
dc.contributor.department	Helmholtz Centre for Infection Research, Braunschweig, Germany.	en_GB
dc.identifier.journal	The FEBS journal	en_GB
refterms.dateFOA	2014-01-15T00:00:00Z
html.description.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.