.png){kind=icon}
.png){kind=icon}
Return
Mixed-class J-domain protein scaffolds promote expanded aggregate handling and multivalent Hsp70 engagement during functional disaggregase assembly
.png){kind=icon}
OA
AI
A
N
DOI：10.1002/1873-3468.70399.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Protein aggregates threaten cellular proteostasis and are linked to aging and disease. In metazoa, aggregate resolution relies on Hsp70-J-domain protein (JDP)-based disaggregases. Previous studies showed human class A and class B JDP assemblies enhance Hsp70-mediated disaggregation, but the underlying mechanism has remained unclear. Using J-domain mutants that impair Hsp70 binding while preserving mixed-class JDP interaction, we show that synergistic disaggregation is lost when either JDP partner cannot engage Hsp70. Size-resolved disaggregation assays further reveal that mixed-class JDP assemblies influence the processing of distinct luciferase aggregate populations, including aggregate species inefficiently handled by either JDP alone. Our findings support a model in which mixed-class JDP assemblies enhance Hsp70 disaggregation through expanded aggregate-processing capacity and multivalent Hsp70 recruitment by both JDP partners.
Keywords:
disaggregase assembly
multivalent Hsp70 recruitment
primate disaggregases
substrate targeting by J-domain protein scaffolds
Journal
IF:
3
Papers:
2.3W
Citations:
3.8W
Organization
Cited Papers