Fig. 5: Characterisation of the binding interaction between chaperones and αS fibrils.
From: The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends
a Conformational compaction of fluorescently labelled Hsc70 upon binding of ATP and ATPγS, as shown by the change in hydrodynamic radius. Binding to ADP preserves the more expanded state. b Binding interaction between fluorescently labelled Hsc70 and its co-chaperones. Binding was observed between Hsc70 and DnaJB1, leading to an increase in hydrodynamic radius. DnaJB1 can bind in absence of ATP and in presence of ATP-γ-S but dissociates from Hsc70 in the presence of ATP due to the fast hydrolysis of ATP. c Binding of Hsc70 to αS fibrils. Hsc70 shows a binding affinity of Kd = 139.0 ± 27.6 nM in the presence of ATP (R2 = 0.98) and a tighter affinity Kd = 47.5 ± 16.0 nM in the presence of DnaJB1 (R2 = 0.96), which triggers hydrolysis of ATP to ADP, thereby leading to lid closure and stronger binding. d Binding of DnaJB1 and Apg2 to αS fibrils. Apg2 did not bind to αS fibrils. DnaJB1 bound to αS fibrils with an affinity of Kd = 246.1 ± 28.1 nM (R2 = 0.98). The concentrations of αS are given with respect to monomer equivalents. Data in b–d are represented as mean ± standard deviation of n = 3 independent experiments.
