Negatively Charged Lipids Are Essential for Functional and Structural Switch of Human 2-Cys Peroxiredoxin II. Issue 5 (2nd March 2018)

• Record Type: Journal Article
• Authors: Haruyama, Takamitsu; Uchihashi, Takayuki; Yamada, Yutaro; Kodera, Noriyuki; Ando, Toshio; Konno, Hiroki
• Is Part Of: Journal of molecular biology. Volume 430:Issue 5(2018)
• Page Start: 602
• Page End: 610
• Publication Date: 2018-03-02
• Subjects: 2-Cys peroxiredoxin -- functional conversion -- lipid–protein assemblies; Prxs peroxiredoxins -- HMW high molecular weight -- PS phosphatidylserine -- PG phosphatidylglycerol -- hPrxII human 2-Cys PrxII -- CysP peroxidatic cysteine -- Trx thioredoxin -- SEC size-exclusion chromatography -- CS citrate synthase -- AFM atomic force microscopy -- PE phosphatidylethanolamine -- PC phosphatidylcholine; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2017.12.020
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: The function of ubiquitous 2-Cys peroxiredoxins (Prxs) can be converted alternatively from peroxidases to molecular chaperones. This conversion has been reported to occur by the formation of high-molecular-weight (HMW) complexes upon overoxidation of or ATP/ADP binding to 2-Cys Prxs, but its mechanism is not well understood. Here, we show that upon binding to phosphatidylserine or phosphatidylglycerol dimeric human 2-Cys PrxII (hPrxII) is assembled to trefoil-shaped small oligomers (possibly hexamers) with full chaperone and null peroxidase activities. Spherical HMW complexes are formed, only when phosphatidylserine or phosphatidylglycerol is bound to overoxidized or ATP/ADP-bound hPrxII. The spherical HMW complexes are lipid vesicles covered with trefoil-shaped oligomers arranged in a hexagonal lattice pattern. Thus, these lipids with a net negative charge, which can be supplied by increased membrane trafficking under oxidative stress, are essential for the structural and functional switch of hPrxII and possibly most 2-Cys Prxs. Graphical abstract: Unlabelled Image Highlights: hPrxII HMW complex formation requires the binding of ADP/ATP and lipid vesicles. Trefoil-shaped hPrxII oligomer is formed by negative charged lipids. Trefoil-shaped hPrxII oligomer converts to HMW complex by ADP/ATP. The functional switch occurs just by the binding of negative charged lipids to hPrxII.