TY  - JOUR
AU  - Ho, Chi-Ting
AU  - Grousl, Tomas
AU  - Shatz, Oren
AU  - Jawed, Areeb
AU  - Ruger-Herreros, Carmen
AU  - Semmelink, Marije
AU  - Zahn, Regina
AU  - Richter, Karsten
AU  - Bukau, Bernd
AU  - Mogk, Axel
TI  - Cellular sequestrases maintain basal Hsp70 capacity ensuring balanced proteostasis.
JO  - Nature Communications
VL  - 10
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2019-02509
SP  - 4851
PY  - 2019
N1  - DKFZ-ZMBH Alliance
AB  - Maintenance of cellular proteostasis is achieved by a multi-layered quality control network, which counteracts the accumulation of misfolded proteins by refolding and degradation pathways. The organized sequestration of misfolded proteins, actively promoted by cellular sequestrases, represents a third strategy of quality control. Here we determine the role of sequestration within the proteostasis network in Saccharomyces cerevisiae and the mechanism by which it occurs. The Hsp42 and Btn2 sequestrases are functionally intertwined with the refolding activity of the Hsp70 system. Sequestration of misfolded proteins by Hsp42 and Btn2 prevents proteostasis collapse and viability loss in cells with limited Hsp70 capacity, likely by shielding Hsp70 from misfolded protein overload. Btn2 has chaperone and sequestrase activity and shares features with small heat shock proteins. During stress recovery Btn2 recruits the Hsp70-Hsp104 disaggregase by directly interacting with the Hsp70 co-chaperone Sis1, thereby shunting sequestered proteins to the refolding pathway.
LB  - PUB:(DE-HGF)16
C6  - pmid:31649258
C2  - pmc:PMC6813348
DO  - DOI:10.1038/s41467-019-12868-1
UR  - https://inrepo02.dkfz.de/record/147392
ER  -