Fig. 6: Emerging principles of Hsc70 disaggregase activity.
From: The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends
Model for Hsc70-mediated protein disaggregation of αS fibrils. This disaggregation mechanism comprises six steps: step 1, DnaJB1 binding to αS fibrils; step 2, Hsc70 loading onto fibrils mediated by DnaJB1; step 3, hydrolysis of Hsc70-bound ATP to ADP and dissociation of DNAJB1; step 4: further Hsc70 loading resulting in clustering of Hsc70 at fibril ends; step 5, Apg2 binding to Hsc70; step 6, dissociation of αS monomer coupled to ADP dissociation from Hsc70 and disassembly of the chaperone machinery.
