Open AccessClass-specific interactions between Sis1 J-domain protein and Hsp70 chaperone potentiate disaggregation of misfolded proteins
Author(s) -
Hubert Wyszkowski,
Anna Janta,
Wiktoria Sztangierska,
Igor Obuchowski,
Tomasz Chamera,
Agnieszka Kłosowska,
Krzysztof Liberek
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2108163118
Subject(s) - chaperone (clinical) , protein folding , proteostasis , biology , hsp70 , protein aggregation , co chaperone , plasma protein binding , microbiology and biotechnology , protein structure , saccharomyces cerevisiae , biochemistry , computational biology , biophysics , yeast , heat shock protein , medicine , pathology , gene
Significance How chaperones rescue cells from toxic aggregates, associated with stress, aging, and disease, is not fully understood. Here, we focus on aggregate recognition by yeast Hsp70- and Hsp104-disaggregating proteins. We show that two conserved classes of J-domain proteins (JDPs/Hsp40s), which regulate Hsp70, use disparate mechanisms to recruit chaperones to aggregates. Bipartite interaction with Hsp70 enables Sis1, a Class B JDP, to tether more Hsp70 molecules to the aggregate, which improves disaggregation with Hsp104. Ydj1 of the Class A, in turn, drives effective reactivation of misfolding-prone substrates. Our results demonstrate that the two classes of JDPs, albeit overlapping in function, differently contribute to the individual stages of disaggregation. This demonstrates how the diversification of cochaperones improves protein quality control.