Study on cold and heat denaturation of amyloid fibrils of intrinsically disordered alpha-synuclein

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18518
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biophysics
• Research Institution: Osaka University
• Principal Investigator: YOUNG-HO LEE 大阪大学, たんぱく質研究所, 講師 (70589431)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: Alpha-synuclein / Amyloid fibril / Cold denaturation / Heat denaturation / Kinetics / Protein aggregation / Protein misfolding / Thermodynamics

Outline of Final Research Achievements

I examined cold and heat denaturation of amyloid fibrils of intrinsically disordered alpha-synuclein (aSN) prepared at various temperatures (298, 310, 323, 333, and 343 K). Despite differences in temperature for aSN amyloidogenesis, all fibrils showed similar core regions and secondary structures with the distinct width. As temperature increased from 298 to 383 K, all types of aSN fibrils heat-denatured to monomers from approximately 343 K. Decreasing temperature from 298 to 273 K caused cold denaturation of fibrils to monomers. Intriguingly, the stability of aSN fibrils depended on temperature for preparing fibrils. aSN fibrils generated at higher temperature showed higher stability at high and low temperature as well as slower denaturation kinetics than fibrils formed at lower temperature. Taken together, the stability of aSN amyloid fibrils depended on growing temperature of fibrils which produced differences in higher order structures of amyloid fibrils.

Free Research Field

蛋白質科学、生物物理、生化学