Bacterial Hsp90 Facilitates the Degradation of Aggregation-Prone Hsp70-Hsp40 Substrates

Bruno Fauvet; Andrija Finka; Marie-Pierre Castanié-Cornet; Anne-Marie Cirinesi; Pierre Genevaux; Manfredo Quadroni; Pierre Goloubinoff

doi:10.3389/fmolb.2021.653073

Bacterial Hsp90 Facilitates the Degradation of Aggregation-Prone Hsp70-Hsp40 Substrates

Front Mol Biosci. 2021 Apr 15:8:653073. doi: 10.3389/fmolb.2021.653073. eCollection 2021.

Authors

Bruno Fauvet¹, Andrija Finka², Marie-Pierre Castanié-Cornet³, Anne-Marie Cirinesi³, Pierre Genevaux³, Manfredo Quadroni⁴, Pierre Goloubinoff¹

Affiliations

¹ Department of Plant Molecular Biology (DBMV), University of Lausanne, Lausanne, Switzerland.
² Department of Ecology, Agronomy and Aquaculture, University of Zadar, Zadar, Croatia.
³ Laboratoire de Microbiologie et de Génétique Moléculaires, Center de Biologie Intégrative, CNRS, Université de Toulouse, Toulouse, France.
⁴ Protein Analysis Facility, University of Lausanne, Lausanne, Switzerland.

Abstract

In eukaryotes, the 90-kDa heat shock proteins (Hsp90s) are profusely studied chaperones that, together with 70-kDa heat shock proteins (Hsp70s), control protein homeostasis. In bacteria, however, the function of Hsp90 (HtpG) and its collaboration with Hsp70 (DnaK) remains poorly characterized. To uncover physiological processes that depend on HtpG and DnaK, we performed comparative quantitative proteomic analyses of insoluble and total protein fractions from unstressed wild-type (WT) Escherichia coli and from knockout mutants ΔdnaKdnaJ (ΔKJ), ΔhtpG (ΔG), and ΔdnaKdnaJΔhtpG (ΔKJG). Whereas the ΔG mutant showed no detectable proteomic differences with wild-type, ΔKJ expressed more chaperones, proteases and ribosomes and expressed dramatically less metabolic and respiratory enzymes. Unexpectedly, we found that the triple mutant ΔKJG showed higher levels of metabolic and respiratory enzymes than ΔKJ, suggesting that bacterial Hsp90 mediates the degradation of aggregation-prone Hsp70-Hsp40 substrates. Further in vivo experiments suggest that such Hsp90-mediated degradation possibly occurs through the HslUV protease.

Keywords: DnaJ; DnaK; HslV; HtpG; chaperones; proteostasis.