Abstract
The Hsp40/Hsp70 chaperone families combine versatile folding capacity with high substrate specificity, which is mainly facilitated by Hsp40s. The structure and function of many Hsp40s remain poorly understood, particularly oligomeric Hsp40s that suppress protein aggregation. Here, we used a combination of biochemical and structural approaches to shed light on the domain interactions of the Hsp40 DnaJB8, and how they may influence recruitment of partner Hsp70s. We identify an interaction between the J-Domain (JD) and C-terminal domain (CTD) of DnaJB8 that sequesters the JD surface, preventing Hsp70 interaction. We propose a model for DnaJB8-Hsp70 recruitment, whereby the JD-CTD interaction of DnaJB8 acts as a reversible switch that can control the binding of Hsp70. These findings suggest that the evolutionarily conserved CTD of DnaJB8 is a regulatory element of chaperone activity in the proteostasis network.
| Original language | English |
|---|---|
| Article number | 946 |
| Journal | Nature Communications |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| State | Published - 11 Feb 2021 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2021, The Author(s).
Funding
This work was supported by grants from the Welch Foundation and the Effie Marie Cain Endowed Scholarship (L.A.J.) and NIGMS R01 GM112678 (P.v.d.W.). We appreciate the help of the Molecular Biophysics Resource core, Structural Biology Laboratory, Biomolecular Nuclear Magnetic Resonance Facility, and Proteomics Core Facility at the University of Texas Southwestern Medical Center. The 750 MHz ssNMR instrument at the University of Pittsburgh was acquired with funding from NIH grant 10 OD012213-01.
| Funders | Funder number |
|---|---|
| National Institutes of Health | |
| NIH Office of the Director | S10OD012213 |
| National Institute of General Medical Sciences | R01 GM112678 |
| Welch Foundation |