Phosphorylation and concomitant structural changes in human 2-Cys peroxiredoxin isotype I differentially regulate its peroxidase and molecular chaperone functions.
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.
Jang
Ho Hee
HH
Environmental Biotechnology National Core Research Center, Gyeongsang National University, Jinju 660-701, Republic of Korea.
Kim
Sun Young
SY
Park
Soo Kwon
SK
Jeon
Hye Sook
HS
Lee
Young Mee
YM
Jung
Ji Hyun
JH
Lee
Sun Yong
SY
Chae
Ho Byoung
HB
Jung
Young Jun
YJ
Lee
Kyun Oh
KO
Lim
Chae Oh
CO
Chung
Woo Sik
WS
Bahk
Jeong Dong
JD
Yun
Dae-Jin
DJ
Cho
Moo Je
MJ
Lee
Sang Yeol
SY
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
D007527:Isoenzymes; D018832:Molecular Chaperones; D006861:Hydrogen Peroxide; D010544:Peroxidases; C504194:2-cys peroxiredoxin, human; D054464:Peroxiredoxins