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Biochemistry. 2017 Mar 7;56(9):1177-1180. doi: 10.1021/acs.biochem.6b01178. Epub 2017 Feb 23.

Inhibition of α-Synuclein Fibril Elongation by Hsp70 Is Governed by a Kinetic Binding Competition between α-Synuclein Species.

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Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
Department of Chemistry and Applied Biosciences, ETH Zurich , Vladimir-Prelog-Weg 1, 8093 Zurich, Switzerland.
Department of Biotechnology and Bioscience, University of Milano-Bicocca , Piazza della Scienza 2, 20126 Milan, Italy.
Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC), University of Zaragoza , 50018 Zaragoza, Spain.


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.

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