The antioxidant protein alkylhydroperoxide reductase of Helicobacter pylori switches from a peroxide reductase to a molecular chaperone function

Abstract

Helicobacter pylori, an oxygen-sensitive microaerophilic bacterium, contains many antioxidant proteins, among which alkylhydroperoxide reductase (AhpC) is the most abundant. The function of AhpC is to protect H. pylori from a hyperoxidative environment by reduction of toxic organic hydroperoxides. We have found that the sequence of AhpC from H. pylori is more homologous to mammalian peroxiredoxins than to eubacterial AhpC. We have also found that the protein structure of AhpC could shift from lowmolecular-weight oligomers with peroxide-reductase activity to high-molecular-weight complexes with molecular-chaperone function under oxidative stresses. Time-course study by following the quaternary structural change of AhpC in vivo revealed that this enzyme changes from low-molecular-weight oligomers under normal microaerobic conditions or short-term oxidative shock to high-molecular-weight complexes after severe long-term oxidative stress. This study revealed that AhpC of H. pylori acts as a peroxide reductase in reducing organic hydroperoxides and as a molecular chaperone for prevention of protein misfolding under oxidative stress.peroxiredoxin ͉ oxidative stress ͉ phylogenetic comparison ͉ dual functionality ͉ quaternary structural change

Distinct Characteristics of Two 2-Cys Peroxiredoxins of Vibrio vulnificus Suggesting Differential Roles in Detoxifying Oxidative Stress

“…3, A and C, and 4A). The overoxidized AhpC of H. pylori can form HMW complexes characteristic of sensitive Prxs under severe oxidative stress, achieving a chaperone activ- ity in vitro (25). In that context, it is tempting to propose that the overoxidized Prx2 would also gain new function(s), such as chaperone activity, enhancing survival of the bacteria under severe oxidative stress, and that the loss of the peroxidase activity would be not wasteful.…”

The Peroxiredoxin Repair Proteins

“…Given the connection between the formation of Prx-SO 2 -and chaperone activity, the report by Chuang et al which proposed that H. pylori AhpC can switch from a peroxide reductase to a molecular chaperone function under oxidative stress was surprising (Chuang et al, 2006). AhpC has not been shown to be substrate inactivated nor does it contain the essential YF-motif Moreover, H. pylori lacks both Srx and sestrin genes.…”

How pH Modulates the Dimer-Decamer Interconversion of 2-Cys Peroxiredoxins from the Prx1 Subfamily

“…Under oxidative stress, some Prx1 subfamily members can be inactivated by C P overoxidation and assume higher-order oligomeric states that display chaperone function as shown in vitro (11,12,14). Besides the redox state, other factors such as post-translational modifications, ionic strength, and pH can also affect the equilibrium of Prx1 oligomers (15).…”