The binding of the small heat-shock protein αB-crystallin to fibrils of α-synuclein is driven by entropic forces

• DOI: 10.1073/pnas.2108790118
• Publication Date: 2021-09-17T17:56:03Z
• Authors: Tom Scheidt; Jacqueline A. Car...; Carl C. Kolbe; Francesco A. Aprile; Olga Tkachenko; Mathias M. J. Bel...; Georg Meisl; Quentin A. E. Peter; Therese W. Herling; Samuel Ness; Marta Castellana-...; Justin L. P. Benesch; Michele Vendruscolo; Christopher M. Do...; Paolo Arosio; Tuomas P. J. Knowles
• Keywords: 0301 basic medicine; Amyloid; 0303 health sciences; Entropy; Microfluidics; aggregation; microfluidics; alpha-Crystallin B Chain; Parkinson Disease; Biological Sciences; Kinetic analysis; Heat-Shock Proteins, Small; 3. Good health; Aggregation; thermodynamic; Protein Aggregates; 03 medical and health sciences; Thermodynamic; Chaperones; kinetic analysis; Proteostasis; alpha-Synuclein; chaperones; Humans; Microfluidics; Aggregation; Chaperones; Thermodynamic; Kinetic analysis

Significance

The formation of amyloid fibrils and toxic oligomeric species has been shown to be inhibited by their interactions with molecular chaperones, thus modulating monomer sequestration and toxicity in the context of neurodegenerative diseases. Understanding the physical and chemical properties underlying chaperone binding processes is essential to explore new therapeutic strategies to target toxic amyloid species. Here, we determine that the binding of the small heat-shock protein

α

B-crystallin to

α

-synculein fibrils, a protein which is related to the progression of Parkinson’s disease, is driven by entropic forces. By applying a microfluidic platform, we accurately quantified the thermodynamics and the kinetics of this intermolecular interaction in the condensed phase and hypothesize that

α

B-crystallin oligomers work as an entropic buffer system.