title: Two endoplasmic reticulum PDI peroxidases increase the efficiency of the use of peroxide during disulfide bond formation.
abstract: Disulfide bond formation in the endoplasmic reticulum by the sulfhydryl oxidase Ero1 family is thought to be accompanied by the concomitant formation of hydrogen peroxide. Since secretory cells can make substantial amounts of proteins that contain disulfide bonds, the production of this reactive oxygen species could have potentially lethal consequences. Here, we show that two human proteins, GPx7 and GPx8, labeled as secreted glutathione peroxidases, are actually endoplasmic reticulum-resident protein disulfide isomerase peroxidases. In vitro, the addition of GPx7 or GPx8 to a folding protein along with protein disulfide isomerase and peroxide enables the efficient oxidative refolding of a reduced denatured protein. Furthermore, both GPx7 and GPx8 interact with Ero1α in vivo, and GPx7 significantly increases oxygen consumption by Ero1α in vitro. Hence, GPx7 and GPx8 may represent a novel route for the productive use of peroxide produced by Ero1α during disulfide bond formation.
authors.affiliation: Department of Biochemistry, University of Oulu, Linnanmaa Campus, 90570 Oulu, Finland.
authors.forename: Van Dat
authors.initials: VD
authors.lastname: Nguyen
authors.forename: Mirva J
authors.initials: MJ
authors.lastname: Saaranen
authors.forename: Anna-Riikka
authors.initials: AR
authors.lastname: Karala
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Lappi
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Irina B
authors.initials: IB
authors.lastname: Raykhel
authors.forename: Heli I
authors.initials: HI
authors.lastname: Alanen
authors.forename: Kirsi E H
authors.initials: KE
authors.lastname: Salo
authors.forename: Chih-Chen
authors.initials: CC
authors.lastname: Wang
authors.forename: Lloyd W
authors.initials: LW
authors.lastname: Ruddock
mesh_terms: D004220:Disulfides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D010545:Peroxides / Q000378:metabolism; D011489:Protein Denaturation; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D017510:Protein Folding; D011499:Protein Processing, Post-Translational
chemical_list: D004220:Disulfides; D010545:Peroxides; D006861:Hydrogen Peroxide; C558642:GPX8 protein, human; D010544:Peroxidases; C558641:GPX7 protein, human; D005979:Glutathione Peroxidase; D019704:Protein Disulfide-Isomerases