Heat of supersaturation-limited amyloid burst directly monitored by isothermal titration calorimetry

Tatsuya Ikenoue, Young Ho Lee, J. Kardos, Hisashi Yagi, Takahisa Ikegami, Hironobu Naiki, Yuji Goto

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Amyloid fibrils form in supersaturated solutions via a nucleation and growth mechanism. Although the structural features of amyloid fibrils have become increasingly clearer, knowledge on the thermodynamics of fibrillation is limited. Furthermore, protein aggregation is not a target of calorimetry, one of the most powerful approaches used to study proteins. Here, with â2-microglobulin, a protein responsible for dialysis-related amyloidosis, we show direct heat measurements of the formation of amyloid fibrils using isothermal titration calorimetry (ITC). The spontaneous fibrillation after a lag phase was accompanied by exothermic heat. The thermodynamic parameters of fibrillation obtained under various protein concentrations and temperatures were consistent with the main-chain dominated structural model of fibrils, in which overall packing was less than that of the native structures. We also characterized the thermodynamics of amorphous aggregation, enabling the comparison of protein folding, amyloid fibrillation, and amorphous aggregation. These results indicate that ITC will become a promising approach for clarifying comprehensively the thermodynamics of protein folding and misfolding.

Original languageEnglish
Pages (from-to)6654-6659
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number18
DOIs
Publication statusPublished - May 6 2014

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Calorimetry
Thermodynamics
Amyloid
Hot Temperature
Protein Folding
Proteins
Structural Models
Amyloidosis
Dialysis
Temperature
Growth

Keywords

  • Enthalpy change
  • Metastability
  • Solubility
  • Thermodynamic stability
  • Thioflavin T

ASJC Scopus subject areas

  • General

Cite this

Heat of supersaturation-limited amyloid burst directly monitored by isothermal titration calorimetry. / Ikenoue, Tatsuya; Lee, Young Ho; Kardos, J.; Yagi, Hisashi; Ikegami, Takahisa; Naiki, Hironobu; Goto, Yuji.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 18, 06.05.2014, p. 6654-6659.

Research output: Contribution to journalArticle

Ikenoue, Tatsuya ; Lee, Young Ho ; Kardos, J. ; Yagi, Hisashi ; Ikegami, Takahisa ; Naiki, Hironobu ; Goto, Yuji. / Heat of supersaturation-limited amyloid burst directly monitored by isothermal titration calorimetry. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 18. pp. 6654-6659.
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