title: Phosphorylation and concomitant structural changes in human 2-Cys peroxiredoxin isotype I differentially regulate its peroxidase and molecular chaperone functions.
abstract: The H2O2-catabolizing peroxidase activity of human peroxiredoxin I (hPrxI) was previously shown to be regulated by phosphorylation of Thr90. Here, we show that hPrxI forms multiple oligomers with distinct secondary structures. HPrxI is a dual function protein, since it can behave either as a peroxidase or as a molecular chaperone. The effects of phosphorylation of hPrxI on its protein structure and dual functions were determined using site-directed mutagenesis, in which the phosphorylation site was substituted with aspartate to mimic the phosphorylated status of the protein (T90D-hPrxI). Phosphorylation of the protein induces significant changes in its protein structure from low molecular weight (MW) protein species to high MW protein complexes as well as its dual functions. In contrast to the wild type (WT)- and T90A-hPrxI, the T90D-hPrxI exhibited a markedly reduced peroxidase activity, but showed about sixfold higher chaperone activity than WT-hPrxI.
authors.affiliation: Environmental Biotechnology National Core Research Center, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Ho Hee
authors.initials: HH
authors.lastname: Jang
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Soo Kwon
authors.initials: SK
authors.lastname: Park
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Jeon
authors.forename: Young Mee
authors.initials: YM
authors.lastname: Lee
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Jung
authors.forename: Sun Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Ho Byoung
authors.initials: HB
authors.lastname: Chae
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Jung
authors.forename: Kyun Oh
authors.initials: KO
authors.lastname: Lee
authors.forename: Chae Oh
authors.initials: CO
authors.lastname: Lim
authors.forename: Woo Sik
authors.initials: WS
authors.lastname: Chung
authors.forename: Jeong Dong
authors.initials: JD
authors.lastname: Bahk
authors.forename: Dae-Jin
authors.initials: DJ
authors.lastname: Yun
authors.forename: Moo Je
authors.initials: MJ
authors.lastname: Cho
authors.forename: Sang Yeol
authors.initials: SY
authors.lastname: Lee
mesh_terms: D019943:Amino Acid Substitution; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010544:Peroxidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054464:Peroxiredoxins; D010766:Phosphorylation; D017354:Point Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D007527:Isoenzymes; D018832:Molecular Chaperones; D006861:Hydrogen Peroxide; D010544:Peroxidases; C504194:2-cys peroxiredoxin, human; D054464:Peroxiredoxins