Cold denaturation of α-synuclein amyloid fibrils

Tatsuya Ikenoue, Young Ho Lee, J. Kardos, Miyu Saiki, Hisashi Yagi, Yasushi Kawata, Yuji Goto

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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. Chilling stress causes stable α-synuclein fibrils to dissociate into monomers. Monomers detach directly from the fibril ends. Amyloid-specific charge repulsion caused by the burial of charged residues in fibril cores induces cold denaturation of α-synuclein fibrils. At elevated temperatures, the dissociation of monomers from fibril ends also takes place, which is further amplified by fibril breakage.

Original languageEnglish
Pages (from-to)7799-7804
Number of pages6
JournalAngewandte Chemie - International Edition
Volume53
Issue number30
DOIs
Publication statusPublished - Jul 21 2014

Fingerprint

Synucleins
Denaturation
Amyloid
Burial
Hot Temperature
Monomers
Chilling
Protein folding
Temperature
Insulin
Protein Folding
Pathology
Peptides
Specific heat
Enthalpy
Thermodynamic stability
Proteins

Keywords

  • aggregation
  • amyloid fibrils
  • calorimetry
  • denaturation
  • protein misfolding

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Medicine(all)

Cite this

Ikenoue, T., Lee, Y. H., Kardos, J., Saiki, M., Yagi, H., Kawata, Y., & Goto, Y. (2014). Cold denaturation of α-synuclein amyloid fibrils. Angewandte Chemie - International Edition, 53(30), 7799-7804. https://doi.org/10.1002/anie.201403815

Cold denaturation of α-synuclein amyloid fibrils. / Ikenoue, Tatsuya; Lee, Young Ho; Kardos, J.; Saiki, Miyu; Yagi, Hisashi; Kawata, Yasushi; Goto, Yuji.

In: Angewandte Chemie - International Edition, Vol. 53, No. 30, 21.07.2014, p. 7799-7804.

Research output: Contribution to journalArticle

Ikenoue, T, Lee, YH, Kardos, J, Saiki, M, Yagi, H, Kawata, Y & Goto, Y 2014, 'Cold denaturation of α-synuclein amyloid fibrils', Angewandte Chemie - International Edition, vol. 53, no. 30, pp. 7799-7804. https://doi.org/10.1002/anie.201403815
Ikenoue, Tatsuya ; Lee, Young Ho ; Kardos, J. ; Saiki, Miyu ; Yagi, Hisashi ; Kawata, Yasushi ; Goto, Yuji. / Cold denaturation of α-synuclein amyloid fibrils. In: Angewandte Chemie - International Edition. 2014 ; Vol. 53, No. 30. pp. 7799-7804.
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