Kinetics and thermodynamics of amyloid formation from direct measurements of fluctuations in fibril mass
| Autor: | Tuomas P. J. Knowles, Mark E. Welland, Glyn L. Devlin, Stefan Auer, Wenmiao Shu, Christopher M. Dobson, Sarah Meehan |
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| Rok vydání: | 2007 |
| Předmět: |
Amyloid
Protein Denaturation Circular dichroism Surface Properties Kinetics Thermodynamics Biosensing Techniques Protein aggregation Microscopy Atomic Force Fibril Models Biological Heat shock protein Humans Hypoglycemic Agents Insulin Heat-Shock Proteins Multidisciplinary Chemistry Circular Dichroism Temperature Quartz crystal microbalance Hydrogen-Ion Concentration Biological Sciences Molecular Weight Solutions Gold Chemical chaperone |
| Zdroj: | Proceedings of the National Academy of Sciences. 104:10016-10021 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Aggregation of proteins and peptides is a widespread and much-studied problem, with serious implications in contexts ranging from biotechnology to human disease. An understanding of the proliferation of such aggregates under specific conditions requires a quantitative knowledge of the kinetics and thermodynamics of their formation; measurements that to date have remained elusive. Here, we show that precise determination of the growth rates of ordered protein aggregates such as amyloid fibrils can be achieved through real–time monitoring, using a quartz crystal oscillator, of the changes in the numbers of molecules in the fibrils from variations in their masses. We show further that this approach allows the effect of other molecular species on fibril growth to be characterized quantitatively. This method is widely applicable, and we illustrate its power by exploring the free-energy landscape associated with the conversion of the protein insulin to its amyloid form and elucidate the role of a chemical chaperone and a small heat shock protein in inhibiting the aggregation reaction. |
| Databáze: | OpenAIRE |
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