title: A thermodynamic analysis of fibrillar polymorphism.
abstract: 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 DeltaC(p) determined by isothermal titration calorimetry. Sulfate fibrils show a negative DeltaC(p) expected from a folding reaction, while the DeltaC(p) for glycine fibrils is essentially zero. NaCl fibrils, which are less stable than the other fibrils, have a large and positive C(p). The predicted change in solvent accessible area is not a useful predictor of fibrillar DeltaC(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 C(p). These results highlight differences in the driving forces of native folding and fibril formation.
authors.affiliation: Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Centre, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Jeppesen
authors.forename: Kim
authors.initials: K
authors.lastname: Hein
authors.forename: Poul
authors.initials: P
authors.lastname: Nissen
authors.forename: Peter
authors.initials: P
authors.lastname: Westh
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Otzen
mesh_terms: D000595:Amino Acid Sequence; D002151:Calorimetry; D002942:Circular Dichroism; D005934:Glucagon / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012965:Sodium Chloride / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D013431:Sulfates; D012965:Sodium Chloride; D005934:Glucagon; D010196:Pancreatic Elastase; D005998:Glycine