A thermodynamic analysis of fibrillar polymorphism

作者：Jeppesen Martin D; Hein Kim; Nissen Poul; Westh Peter; Otzen Daniel E^*

来源：Biophysical Chemistry, 2010, 149(1-2): 40-46.

DOI：10.1016/j.bpc.2010.03.016

• Glucagon
• Fibrillation
• Isothermal titration calorimetry
• Fiber diffraction
• Circular dichroism

We explore the thermodynamic properties of three different fibrils of the peptide hormone glucagon, formed under different salt conditions (glycine, sulfate and NaCl. respectively), and differing considerably in compactness. The three fibrils display a large variation in the specific heat capacity Delta C(p) determined by isothermal titration calorimetry. Sulfate fibrils show a negative Delta C(p) expected from a folding reaction, while the Delta C(p) for glycine fibrils is essentially zero. NaCl fibrils, which are less stable than the other fibrils, have a large and positive Delta C(p). The predicted change in solvent accessible area is not a useful predictor of fibrillar Delta C(p) unlike the case for globular proteins. We speculate that strong backbone interactions may lead to the unfavorable burial of polar side residues, water and/or charged groups which all can have major influence on the change in Delta C(p). These results highlight differences in the driving forces of native folding and fibril formation.

• 出版日期2010-6