The influence of phospholipid membranes on bovine calcitonin secondary structure and amyloid formation.
Calcitonin, a peptide hormone associated with medullary carcinoma of the thyroid, has the potential to form amyloid fibrils and may be a valuable model for investigating the role of peptide-membrane interactions in beta-sheet and amyloid formation. Via a new model peptide system, bovine calcitonin, we found that the exposure of peptide to phospholipid membranes altered its structure relative to the structures formed in aqueous solutions. Of particular relevance to the amyloidoses, incubation of calcitonin with cholesterol-rich and ganglioside-containing membranes resulted in significant enrichment in the beta-sheet and amyloid content of the peptide. The formation of amyloid was also accelerated in these systems. A correlation between the phospholipid-induced structural alterations and calcitonin binding affinities to phospholipid membranes was evident. Bovine calcitonin has considerably higher binding affinity for the phospholipid systems that enhanced its beta-sheet and amyloid structure. Electrostatic forces were not the governing forces behind the observed behavior, as supported by the fact that the ionic strength did not affect the peptide structures or binding affinities. A Van't Hoff analysis of the temperature-dependent peptide binding affinities indicated that binding led to an increase in enthalpy and possibly an increase in entropy of the peptide-membrane systems. Experiments with other amyloid-forming peptides such as beta-amyloid of Alzheimer's disease have also shown similar results and may indicate the need to manipulate peptide-membrane interactions in order to control amyloid formation and its associated disease.
Wang
Steven S-S
SS
Department of Chemical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, Taiwan 10617. sswang@ntu.edu.tw
Good
Theresa A
TA
Rymer
Dawn L
DL
D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D002116:Calcitonin / Q000737:chemistry*; D002417:Cattle; D008567:Membranes, Artificial; D010743:Phospholipids / Q000737:chemistry*; D017433:Protein Structure, Secondary
D000682:Amyloid; D008567:Membranes, Artificial; D010743:Phospholipids; D002116:Calcitonin