Negatively Charged Lipids Are Essential for Functional and Structural Switch of Human 2-Cys Peroxiredoxin II

• Published in: Journal of molecular biology Vol. 430; no. 5; pp. 602 - 610
• Main Authors: Haruyama, Takamitsu, Uchihashi, Takayuki, Yamada, Yutaro, Kodera, Noriyuki, Ando, Toshio, Konno, Hiroki
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 02.03.2018
• Subjects: 2-Cys peroxiredoxin; functional conversion; lipid–protein assemblies; lipid–protein assemblies; PS; 2-Cys peroxiredoxin; AFM; functional conversion; SEC; CS; HMW; CysP; PC; PE; PG; hPrxII; Prxs; Trx
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2017.12.020

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. [Display omitted] •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.