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Synthesis of Cyclic Polymers and Characterization of Their Diffusive Motion in the Melt State at the Single Molecule Level
Published on: September 26, 2016
A thermodynamic analysis of fibrillar polymorphism
Martin D Jeppesen1, Kim Hein, Poul Nissen
1Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Centre, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
Biophysical Chemistry
|May 4, 2010
Summary
Glucagon fibrils formed in different salt conditions exhibit varied thermodynamic properties, particularly specific heat capacity (ΔCp). These findings reveal distinct driving forces between protein folding and fibril formation.
Area of Science:
- Biophysics
- Thermodynamics
- Protein Chemistry
Background:
- The peptide hormone glucagon can form amyloid fibrils implicated in diseases.
- Fibril formation involves complex thermodynamic changes that differ from native protein folding.
Purpose of the Study:
- To investigate the thermodynamic properties, specifically heat capacity (ΔCp), of glucagon fibrils formed under varying salt conditions.
- To compare the thermodynamic behavior of glucagon fibrils with that of globular proteins and native protein folding.
Main Methods:
- Isothermal titration calorimetry (ITC) was used to determine the specific heat capacity (ΔCp) of three distinct glucagon fibril types.
- Fibrils were prepared under different salt conditions: glycine, sulfate, and NaCl.
Main Results:
- Significant variations in ΔCp were observed among the three glucagon fibril types.
- Sulfate fibrils exhibited a negative ΔCp, consistent with folding reactions.
- Glycine fibrils showed a near-zero ΔCp, while NaCl fibrils displayed a large positive ΔCp and lower stability.
- Predicted changes in solvent accessible area were poor predictors of fibrillar ΔCp, unlike in globular proteins.
Conclusions:
- The thermodynamic properties of glucagon fibrils are highly dependent on formation conditions (salt type).
- Unfavorable burial of polar/charged groups and strong backbone interactions likely influence fibril ΔCp.
- Driving forces for fibril formation differ substantially from those governing native protein folding.
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