Thermodynamics of amyloid dissociation provide insights into aggregate stability regimes
| Autor: | Jacob L. Jordan, Christopher J. Roberts, Jennifer M. Andrews, Rebecca K. Brummitt, Erik J. Fernandez |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Amyloid
Protein Denaturation Biophysics Thermodynamics Thermodynamic integration Calorimetry Kinetic energy Biochemistry Dissociation (chemistry) chemistry.chemical_compound Urea chemistry.chemical_classification Quantitative Biology::Biomolecules Protein Stability Circular Dichroism Organic Chemistry Temperature Polymer Chymotrypsinogen Kinetics Monomer chemistry Chemical stability |
| Zdroj: | Biophysical Chemistry. :10-18 |
| ISSN: | 0301-4622 |
| DOI: | 10.1016/j.bpc.2012.06.001 |
| Popis: | Amyloid aggregates have been hypothesized as a global low free energy state for proteins at finite concentrations. Near its midpoint unfolding temperature, α-chymotrypsinogen A (aCgn) spontaneously forms amyloid polymers, indicating the free energy of aggregates (A) is significantly lower than that for unfolded (U) and native (N) monomers at those particular conditions. The relative thermodynamic stability of A, U, and N states was estimated semi-quantitatively as a function of temperature (T) and [urea] via a combination of calorimetry, urea-assisted unfolding and dissociation, aggregation kinetics, and changes in solvent-exposed surface area, combined with thermodynamic integration and a linear transfer free energy model. The results at first suggest that N is more thermodynamically stable than A at sufficiently low T and [urea], but this may be convoluted with kinetic effects. Interestingly, the kinetic stability of aggregates highlights that the practical measure of stability may be the free energy barrier(s) between A and U, as U serves as a key intermediate between N and A states. |
| Databáze: | OpenAIRE |
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