Inhibition of α-Synuclein Fibril Elongation by Hsp70 Is Governed by a Kinetic Binding Competition between α-Synuclein Species
| Autor: | Tuomas P. J. Knowles, Janet R. Kumita, Anne Dhulesia, Christopher M. Dobson, Giuliana Fusco, Paolo Arosio, Paolo Tortora, Francesco A. Aprile, Serene W. Chen, Nunilo Cremades, Michele Vendruscolo |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Aprile, Francesco [0000-0002-5040-4420], Kumita, Janet [0000-0002-3887-4964], Knowles, Tuomas [0000-0002-7879-0140], Vendruscolo, Michele [0000-0002-3616-1610], Apollo - University of Cambridge Repository, Aprile, F, Arosio, P, Fusco, G, Chen, S, Kumita, J, Dhulesia, A, Tortora, P, Knowles, T, Vendruscolo, M, Dobson, C, Cremades, N |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Kinetics Cell Biology Protein aggregation Fibril Biochemistry Binding Competitive Protein Structure Secondary Substrate Specificity 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Humans HSP70 Heat-Shock Proteins Kinetic Alpha-synuclein HSP70 Heat-Shock Protein Binding protein Neurodegeneration medicine.disease Hsp70 030104 developmental biology medicine.anatomical_structure chemistry Biophysics alpha-Synuclein Protein Multimerization 030217 neurology & neurosurgery Human |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | The Hsp70 family of chaperones plays an essential role in suppressing protein aggregation in the cell. Here we investigate the factors controlling the intrinsic ability of human Hsp70 to inhibit the elongation of amyloid fibrils formed by the Parkinson's disease-related protein α-synuclein. Using kinetic analysis, we show that Hsp70 binds preferentially to α-synuclein fibrils as a consequence of variations in the association and dissociation rate constants of binding to the different aggregated states of the protein. Our findings illustrate the importance of the kinetics of binding of molecular chaperones, and also of potential therapeutic molecules, in the efficient suppression of specific pathogenic events linked to neurodegeneration. |
| Databáze: | OpenAIRE |
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