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New Swiss-knife activities of GroEL/Hsp60 proteins

Zhou, Z.; Yang, D.; Lambert, I.; Decroo, C.; Mascolo, C.; Heidig, S.-L.; Karasiewicz, T.; Flot, J.-F.; Prevost, M.; Wattiez, R.; Vandenbussche, G.; Fontaine, V.

2025-07-07 biochemistry
10.1101/2025.07.07.663466 bioRxiv
Show abstract

GroEL/Hsp60 chaperonins are key proteins that control cell metabolism, stress adaptation and survival. They usually form a tetradecameric structure that assists, coupled to ATP hydrolysis, 10% of all cellular protein folding. Using recombinant E. coli, human mitochondrial and M. tuberculosis chaperonins, we found that these proteins have thioesterase, esterase and even, for some of them, auto-acyltransferase activities. The smaller oligomers of Hsp60 and M. tuberculosis GroEL1 were more prone to use the long acyl carbon chain substrate palmitoyl-CoA compared to tetradecameric E. coli GroEL and Hsp60. Enzymatic competition and replacement of M. tuberculosis GroEL1 residues allow identifying Asp86 and Thr89 in the ATP-binding pocket and an additional Ser393 influencing the thioesterase activity. Additionally, M. tuberculosis GroEL1 might enhance palmitoylation of the PpsE protein, which plays a role in the phthiocerol dimycocerosate (PDIM) biosynthesis. This could explain at least partly the involvement of GroEL1 in PDIM biosynthesis and antibiotic resistance.

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