Details
| Original language | English |
|---|---|
| Pages (from-to) | 83-92 |
| Number of pages | 10 |
| Journal | FEBS Journal |
| Volume | 280 |
| Issue number | 1 |
| Early online date | 2 Nov 2012 |
| Publication status | Published - 3 Jan 2013 |
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.
Keywords
- bone morphogenetic protein-2 (BMP-2), cystine knot, kinetics, protein folding and dimerization, TGF-β family
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology
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In: FEBS Journal, Vol. 280, No. 1, 03.01.2013, p. 83-92.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Folding and dimerization kinetics of bone morphogenetic protein-2, a member of the transforming growth factor-β family
AU - Vallejo, Luis F.
AU - Rinas, Ursula
PY - 2013/1/3
Y1 - 2013/1/3
N2 - 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.
AB - 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.
KW - bone morphogenetic protein-2 (BMP-2)
KW - cystine knot
KW - kinetics
KW - protein folding and dimerization
KW - TGF-β family
UR - http://www.scopus.com/inward/record.url?scp=84872022338&partnerID=8YFLogxK
U2 - 10.1111/febs.12051
DO - 10.1111/febs.12051
M3 - Article
C2 - 23122408
AN - SCOPUS:84872022338
VL - 280
SP - 83
EP - 92
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 1
ER -