Direct Measurement of the Thermodynamic Parameters of Amyloid Formation by Isothermal Titration Calorimetry

Amyloid fibril deposition is associated with over 20 degenerative diseases, including Alzheimer's, Parkinson's, and prion diseases. Although research over the last few years has revealed the morphology and structural features of the amyloid form, knowledge about the thermodynamics of amylo...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2004-12, Vol.279 (53), p.55308-55314
Main Authors: Kardos, József, Yamamoto, Kaori, Hasegawa, Kazuhiro, Naiki, Hironobu, Goto, Yuji
Format: Article
Language:English
Subjects:
Amyloid - chemistry
beta 2-Microglobulin - metabolism
Calorimetry - methods
Circular Dichroism
Entropy
Hot Temperature
Humans
Hydrogen-Ion Concentration
Kinetics
Microscopy, Electron
Models, Chemical
Protein Conformation
Protein Denaturation
Protein Folding
Protein Structure, Secondary
Recombinant Proteins - chemistry
Temperature
Thermodynamics
Time Factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Amyloid fibril deposition is associated with over 20 degenerative diseases, including Alzheimer's, Parkinson's, and prion diseases. Although research over the last few years has revealed the morphology and structural features of the amyloid form, knowledge about the thermodynamics of amyloid formation is limited. Here, we report for the first time a direct thermodynamic study of amyloid formation using isothermal titration calorimetry. β2-Microglobulin, a protein responsible for dialysis-related amyloidosis, was used for extending amyloid fibrils in a seed-controlled reaction in the cell of the calorimeter. We investigated the enthalpy and heat capacity changes of the reaction, where the monomeric, acid-denatured molecules adopt an ordered, cross-β-sheet structure in the rigid amyloid fibrils. Despite the dramatic difference in morphology, β2-microglobulin exhibited a similar heat capacity change upon amyloid formation to that of the folding to the native globular state, whereas the enthalpy change of the reaction proved to be markedly lower. In comparison with the native state, the results outline the important structural features of the amyloid fibrils: a similar extent of surface burial even with the supramolecular architecture of amyloid fibrils, a lower level of internal packing, and the possible presence of unfavorable side chain contributions.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M409677200