Mixed‐class J‐domain protein scaffolds promote expanded aggregate handling and multivalent Hsp70 engagement during functional disaggregase assembly
Year: 2026
Type: article
Abstract: 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.
Source: FEBS Letters
Authors: Anna Szlachcic, Nadinath B. Nillegoda
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,980
OpenAlex ID: W7166108252