[Project supported by FrenchBIC] Lisa ZUILY : Regulation of Zn-binding molecular chaperones by Cu, molecular insights?
Lisa ZUILY, from the Institut de Microbiologie de la Méditerranée (laboratoire de Bioénergétique et Ingénierie des Protéines), spent two weeks in the lab of Dr. Olivier Sénèque, from the Laboratoire Chimie et Biologie des Métaux (CEA-Grenoble). This project was supported by a grant from FrenchBIC.
During my Ph.D. I have been exploring the impact of copper, a very powerful antimicrobial reagent, on proteostasis and the role played by molecular chaperone during copper stress. I specially focused on a redox-regulated holdase chaperone : Hsp33. Hsp33 activation is regulated by a zinc center, in which the Zn2+ ion is coordinated by four highly conserved cysteines. Upon oxidative and unfolding stress (e.g., H2O2 and heat), these conserved cysteines form 2 disulfide bonds and zinc is released. This event and the unfolding of the C-terminal region of Hsp33’s allow the exposure of substrate binding site. In presence of copper, Hsp33 can also be activated without the requirement of a thermal stress. To decipher how copper triggers the chaperone activity of Hsp33 at a molecular level, I spent two weeks in O. Sénèque laboratory in Grenoble who has strong expertise on metalloproteins zinc sites reactivity and has access to various spectroscopy approaches : UV absorption, fluorescence and CD. These technics were used to monitor Hsp33 Zn release, Cu binding and changes in the folding of the protein. I would like to acknowledge the FrenchBIC for the grant and Dr. Sénèque, for this great opportunity. Being in his lab was a great experience that taught me a lot.
Publication : “Copper Induces Protein Aggregation, a Toxic Process Compensated by Molecular Chaperones”, mBio, 2022 10.1128/mbio.03251-21