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bioRxiv · 10.1101/2024.05.15.594092

Dicarboxylic acids synergize with yeast and human Hsp60/10 systems to mimic GroEL/ES

Gautam, D.·Aaquib, M.·Kochar, M.·Chakraborty, K.
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Abstract

GroEL/ES has been the archetype to understand the function of the class I chaperonins (Hsp60/10 systems). While very similar in structure, the human or yeast mitochondrial one has diminished negative charge density in the central cavity. These chaperones had also lost their ability to assist a substrate of E.coli GroEL/ES. Here, we show that the eukaryotic Hsp60/10 systems can synergize with dicarboxylic acids in vitro at the physiological concentration of these metabolites to mimic the activity of E. coli GroEL/ES. Combining these Hsp60/10s and metabolites effectively alters the folding landscape like GroEL/ES; this is specific for the eukaryotic chaperonins and not the prokaryotic homologs with less negatively charged cavities. Thus, we identify a potential cooperation between molecular and chemical chaperones that may have important physiological implications linking metabolism to proteostasis.

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Gautam, D., Aaquib, M., Kochar, M., Chakraborty, K.. 2024-05-15. Dicarboxylic acids synergize with yeast and human Hsp60/10 systems to mimic GroEL/ES. https://doi.org/10.1101/2024.05.15.594092

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