A novel reaction of peroxiredoxin 4 towards substrates in oxidative protein folding

Li Zhu; Kai Yang; Xi'e Wang; Xi Wang; Chih-chen Wang

doi:10.1371/journal.pone.0105529

A novel reaction of peroxiredoxin 4 towards substrates in oxidative protein folding

PLoS One. 2014 Aug 19;9(8):e105529. doi: 10.1371/journal.pone.0105529. eCollection 2014.

Authors

Li Zhu¹, Kai Yang¹, Xi'e Wang², Xi Wang², Chih-chen Wang²

Affiliations

¹ National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
² National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Abstract

Peroxiredoxin 4 (Prx4) is the only endoplasmic reticulum localized peroxiredoxin. It functions not only to eliminate peroxide but also to promote oxidative protein folding via oxidizing protein disulfide isomerase (PDI). In Prx4-mediated oxidative protein folding we discovered a new reaction that the sulfenic acid form of Prx4 can directly react with thiols in folding substrates, resulting in non-native disulfide cross-linking and aggregation. We also found that PDI can inhibit this reaction by exerting its reductase and chaperone activities. This discovery discloses an off-pathway reaction in the Prx4-mediated oxidative protein folding and the quality control role of PDI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Endoplasmic Reticulum / metabolism
Humans
Oxidation-Reduction
Oxidoreductases / metabolism
Peroxiredoxins / metabolism*
Protein Binding / physiology
Protein Disulfide-Isomerases / metabolism
Protein Folding

Substances

Oxidoreductases
PRDX4 protein, human
Peroxiredoxins
Protein Disulfide-Isomerases

Grants and funding

This work was supported by grants from the Chinese Ministry of Science and Technology (2011CB910303 and 2012CB911002, http://www.most.gov.cn) and the National Natural Science Foundation of China (31370758, http://www.nsfc.gov.cn). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.