TY - JOUR
T1 - Regulatory inter-domain interactions influence Hsp70 recruitment to the DnaJB8 chaperone
AU - Ryder, Bryan D.
AU - Matlahov, Irina
AU - Bali, Sofia
AU - Vaquer-Alicea, Jaime
AU - van der Wel, Patrick C.A.
AU - Joachimiak, Lukasz A.
N1 - Funding Information:
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.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-021-21147-x
DO - 10.1038/s41467-021-21147-x
M3 - Article
C2 - 33574241
AN - SCOPUS:85101165552
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 946
ER -