Synergistic cooperation of PDI family members in peroxiredoxin 4-driven oxidative protein folding

Yoshimi Sato, Rieko Kojima, Masaki Okumura, Masatoshi Hagiwara, Shoji Masui, Ken Ichi Maegawa, Masatoshi Saiki, Tomohisa Horibe, Mamoru Suzuki, Kenji Inaba

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64 Citations (Scopus)

Abstract

The mammalian endoplasmic reticulum (ER) harbors disulfide bond-generating enzymes, including Ero1α and peroxiredoxin 4 (Prx4), and nearly 20 members of the protein disulfide isomerase family (PDIs), which together constitute a suitable environment for oxidative protein folding. Here, we clarified the Prx4 preferential recognition of two PDI family proteins, P5 and ERp46, and the mode of interaction between Prx4 and P5 thioredoxin domain. Detailed analyses of oxidative folding catalyzed by the reconstituted Prx4-PDIs pathways demonstrated that, while P5 and ERp46 are dedicated to rapid, but promiscuous, disulfide introduction, PDI is an efficient proofreader of non-native disulfides. Remarkably, the Prx4-dependent formation of native disulfide bonds was accelerated when PDI was combined with ERp46 or P5, suggesting that PDIs work synergistically to increase the rate and fidelity of oxidative protein folding. Thus, the mammalian ER seems to contain highly systematized oxidative networks for the efficient production of large quantities of secretory proteins.

Original languageEnglish
Article number2456
JournalScientific reports
Volume3
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • General

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    Sato, Y., Kojima, R., Okumura, M., Hagiwara, M., Masui, S., Maegawa, K. I., Saiki, M., Horibe, T., Suzuki, M., & Inaba, K. (2013). Synergistic cooperation of PDI family members in peroxiredoxin 4-driven oxidative protein folding. Scientific reports, 3, [2456]. https://doi.org/10.1038/srep02456