In vivo parameters influencing 2-Cys Prx oligomerization: The role of enzyme sulfinylation

Redox Biology
Y NoichriMichel B Toledano

Abstract

2-Cys Prxs are H2O2-specific antioxidants that become inactivated by enzyme hyperoxidation at elevated H2O2 levels. Although hyperoxidation restricts the antioxidant physiological role of these enzymes, it also allows the enzyme to become an efficient chaperone holdase. The critical molecular event allowing the peroxidase to chaperone switch is thought to be the enzyme assembly into high molecular weight (HMW) structures brought about by enzyme hyperoxidation. How hyperoxidation promotes HMW assembly is not well understood and Prx mutants allowing disentangling its peroxidase and chaperone functions are lacking. To begin addressing the link between enzyme hyperoxidation and HMW structures formation, we have evaluated the in vivo 2-Cys Prxs quaternary structure changes induced by H2O2 by size exclusion chromatography (SEC) on crude lysates, using wild type (Wt) untagged and Myc-tagged S. cerevisiae 2-Cys Prx Tsa1 and derivative Tsa1 mutants or genetic conditions known to inactivate peroxidase or chaperone activity or altering the enzyme sensitivity to hyperoxidation. Our data confirm the strict causative link between H2O2-induced hyperoxidation and HMW formation/stabilization, also raising the question of whether CP hyperoxidati...Continue Reading

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Citations

Jan 28, 2016·Molecules and Cells·Michel B Toledano, Bo Huang
Jan 27, 2016·Molecules and Cells·Koen Van Laer, Tobias P Dick
Mar 24, 2016·Molecular and Biochemical Parasitology·Francesco AngelucciAndrea Bellelli
Jun 9, 2017·Antioxidants & Redox Signaling·Michael LiebthalKarl-Josef Dietz
Apr 11, 2018·Antioxidants & Redox Signaling·David YoungJoris Messens
Jan 6, 2019·Antioxidants·Tom E ForshawCristina M Furdui
Sep 30, 2020·Biological Chemistry·Kathrin UlrichUrsula Jakob
May 5, 2020·ACS Catalysis·Alexandre KriznikSophie Rahuel-Clermont
Nov 14, 2019·Journal of Chemical Information and Modeling·J A SemelakD A Estrin
Jan 8, 2021·Bioconjugate Chemistry·Matteo ArdiniFrancesco Angelucci

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Methods Mentioned

BETA
size exclusion chromatography
transmission electron microscopy

Software Mentioned

Odyssey

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