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pH effects on the stability and dimerization of procaspase-3
1Department of Molecular and Structural Biochemistry, 128 Polk Hall, North Carolina State University, Raleigh, NC 27695-7622, USA.
Protein Science : a Publication of the Protein Society
|December 4, 2004
Summary
Procaspase-3 dimer stability and folding are pH-dependent, dissociating into monomers below pH 5. Dimerization significantly contributes to protein stability, with monomeric forms emerging at lower pH values.
Area of Science:
- Biochemistry
- Structural Biology
- Protein Folding
Background:
- Procaspase-3 undergoes pH-dependent conformational changes affecting its auto-maturation rate.
- Understanding these changes is crucial for elucidating protein stability and function.
Purpose of the Study:
- To investigate the equilibrium unfolding of procaspase-3(C163S) across a pH range (4-8.5).
- To examine pH-dependent folding, stability, and conformational changes of procaspase-3.
Main Methods:
- Studied equilibrium unfolding of procaspase-3(C163S) using circular dichroism and fluorescence emission spectroscopy.
- Analyzed protein behavior as a function of pH and protein concentration.
Main Results:
- Procaspase-3 dimer dissociates into monomers below pH 5, with complete monomerization at pH 4.
- Unfolding proceeds via a four-state process involving dimerization, dissociation, and monomer unfolding.
- Dimerization contributes over 70% to the conformational free energy, with optimal stability around pH 7.
Conclusions:
- Procaspase-3 exhibits significant pH-dependent structural transitions, impacting its stability and oligomeric state.
- The native ensemble shifts from dimer to monomer as pH decreases, resembling monomeric intermediates at higher pH.
- A comprehensive model of monomeric procaspase-3 is emerging from these findings.
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