Hyperoxidized peroxiredoxin 2 interacts with the protein disulfide- isomerase ERp46

Abstract

Prx (peroxiredoxin) 2 protects cells from deleterious oxidative damage. It catalyses the breakdown of hydroperoxides through a highly reactive cysteine residue and has been linked to chaperone activity that promotes cell survival under conditions of oxidative stress. It may also be involved in redox signalling by binding to other proteins. In the present study we have searched for binding partners of Prx2 in H2O2-treated Jurkat and human umbilical vein endothelial cells and discovered that the hyperoxidized form selectively co-precipitated with the protein disulfide-isomerase ERp46. Mutant analyses revealed that loss of the peroxidative cysteine residue of Prx2 also facilitated complex formation with ERp46, even without H2O2 treatment, whereas the resolving cysteine residue of Prx2 was indispensible for the interaction to occur. The complex involved a stable non-covalent interaction that was disassociated by the reduction of intramolecular disulfides in ERp46, or by disruption of the decameric structure of hyperoxidized Prx2. This is the first example of a protein interaction dependent on the hyperoxidized status of a Prx.

Circadian rhythm of hyperoxidized peroxiredoxin II is determined by hemoglobin autoxidation and the 20S proteasome in red blood cells

“…The inverse relation between total and membrane-associated PrxII-SO 2 H suggests that such replacement is not dependent on thermodynamic equilibrium but rather is tightly controlled, likely through binding of PrxII-SO 2 H to as yet unidentified proteins. In what is, to our knowledge, the first example of a protein interaction dependent on the hyperoxidized state of a Prx, the protein disulfide isomerase ERp46 was recently identified as a binding partner of PrxII-SO 2 H in T cells and endothelial cells (33). The role of membrane-localized PrxII-SO 2 H is only speculative at the present time.…”

Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes

“…The catalytic activity of some eukaryotic PRXs is highly sensitive to reversible inhibition by H 2 O 2 -mediated hyperoxidation, and oxidative inactivation of PRXs is considered as a key transient mechanism to allow local H 2 O 2 levels to accumulate and initiate redox-signaling events (11). Additionally, PRXs can directly regulate H 2 O 2 signal transduction through thiol-disul- fide exchange, allowing the oxidative signal to be transferred to other redox sensitive proteins with a lower affinity for H 2 O 2 than PRXs (13,47).…”

“…Recent evidence shows that PRXs participate in direct regulation of intracellular signal transduction pathways (13,47). The catalytic activity of some eukaryotic PRXs is highly sensitive to reversible inhibition by H 2 O 2 -mediated hyperoxidation, and oxidative inactivation of PRXs is considered as a key transient mechanism to allow local H 2 O 2 levels to accumulate and initiate redox-signaling events (11).…”

Interaction of adenanthin with glutathione and thiol enzymes: Selectivity for thioredoxin reductase and inhibition of peroxiredoxin recycling

“…As a result, reduction of the Prxs is inhibited and they accumulate as disulfides following exposure of the cells to low concentrations of H 2 O 2 . (peroxidatic cysteine to serine) mutants were prepared as described [17] with a few modifications.…”