The Role of α-Synuclein–DNAJB6b Coaggregation in Amyloid Suppression

This is the authors' abstract. We don't add key points for this paper.

Chaperones may retard the aggregation of other proteins and increase their solubility. An important goal is a thermodynamic understanding of such an action. Here, the chaperone DNAJB6b (JB6) is found to suppress amyloid formation of the protein α-synuclein (α-syn) leading to a reduced rate of fibril formation and an increase in apparent solubility of α-syn. These findings were reached at mildly acidic pH and with light seeding under conditions where the effect on secondary nucleation is visible. Cryo-transmission electron microscopy (cryo-TEM) imaging reveals that coaggregates of α-syn and JB6 are formed with significantly altered ultrastructure compared to both pure protein fibrils and pure chaperone aggregates. This is further supported by the formation of ThT-negative aggregates and by the depletion of JB6 from solution in the presence of α-syn. The identification of such coaggregates provides a plausible thermodynamic explanation for an increase in α-syn solubility in the presence of JB6; the reduced chemical potential of the chaperone upon formation of coaggregates can compensate for an increased chemical potential of α-syn, and the system as a whole can lower its free energy to sustain an increased free α-syn concentration.