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July 18th, 2025
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Institute Academy for Precision Measurment Science and Technology, CAS
molecular biology
biorxiv

An Unexpected Role of Molecular Chaperones in Regulating the Excited States and Activities of Folded Enzymes

Wang, G.Open in Google Scholar•Bin, Y.Open in Google Scholar•Chen, Y.Open in Google Scholar•Ding, R.Open in Google Scholar•Qi, S.Open in Google Scholar•Zhao, X.Open in Google Scholar•Zhou, G.Open in Google Scholar•Zhang, X.Open in Google Scholar•Hiller, S.Open in Google Scholar•Liu, M.Open in Google Scholaret al.

Emerging evidence suggests that chaperones not only facilitate the folding of nascent polypeptides but also interact with quasi-native or natively folded proteins. However, the biological significance of these interactions remains unclear. In our previous study, we demonstrated that the molecular chaperone-like protein BSA reshapes the energy landscape of folded client proteins, increasing the population of their excited states. Building on this, we further explored chaperone-enzyme interactions and found that chaperones Spy and Hsp70 affected the conformational exchanges of folded lysozyme, leading to increased catalytic activity. Additionally, we observed that the influence of chaperones on enzyme activity extended to other chaperone-enzyme interactions. Molecular chaperones Hsp70, Spy, Hsp104, and Hsp20, enhanced the catalytic activity of diverse enzymes, such as alkaline phosphatase (PHPT1), DNA polymerase from Pyrococcus furiosus (Pfu pol), endonuclease CRISPR-Cas12a/Cas13a, and xylanase. Our findings reveal an unexpected role of chaperones in modulating the activity of folded enzymes, broadening the known functions and mechanisms of molecular chaperones in biological systems. Furthermore, these insights highlight the potential applications of chaperones in enzyme-based biological assays, diagnostics, and biomanufacturing, as well as studying of new roles of upregulated chaperones in systemically modulating cellular biological processes.

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