Cold Denaturation of α‐Synuclein Amyloid Fibrils1. Issue 30 (11th June 2014)

• Record Type: Journal Article
• Authors: Ikenoue, Tatsuya; Lee, Young‐Ho; Kardos, József; Saiki, Miyu; Yagi, Hisashi; Kawata, Yasushi; Goto, Yuji
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 30(2014)
• Page Start: 7799
• Page End: 7804
• Publication Date: 2014-06-11
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201403815
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Although amyloid fibrils are associated with numerous pathologies, their conformational stability remains largely unclear. Herein, we probe the thermal stability of various amyloid fibrils. α‐Synuclein fibrils cold‐denatured to monomers at 0–20 °C and heat‐denatured at 60–110 °C. Meanwhile, the fibrils of β2‐microglobulin, Alzheimer's Aβ1‐40/Aβ1‐42 peptides, and insulin exhibited only heat denaturation, although they showed a decrease in stability at low temperature. A comparison of structural parameters with positive enthalpy and heat capacity changes which showed opposite signs to protein folding suggested that the burial of charged residues in fibril cores contributed to the cold denaturation of α‐synuclein fibrils. We propose that although cold‐denaturation is common to both native proteins and misfolded fibrillar states, the main‐chain dominated amyloid structures may explain amyloid‐specific cold denaturation arising from the unfavorable burial of charged side‐chains in fibril cores.</p> </abstract>