Negatively Charged Lipids Are Essential for Functional and Structural Switch of Human 2-Cys Peroxiredoxin II
Negatively Charged Lipids Are Essential for Functional and Structural Switch of Human 2-Cys Peroxiredoxin II
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带负电荷的脂质对于人 2-Cys 过氧化还原蛋白 II 的功能和结构转换至关重要
DOI：
10.1016/j.jmb.2017.12.020
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发表时间：
2018
影响因子：
5.6
通讯作者：
Konno Hiroki
中科院分区：
文献类型：
--
作者：
Haruyama Takamitsu;Uchihashi Takayuki;Yamada Yutaro;Kodera Noriyuki;Ando Toshio;Konno Hiroki
普遍存在的 2-Cys 过氧化还原蛋白 (Prxs) 的功能可以从过氧化物酶转换为分子伴侣。据报道，这种转化是通过 2-Cys Prxs 过度氧化或 ATP/ADP 与 2-Cys Prxs 结合形成高分子量 (HMW) 复合物而发生的，但其机制尚不清楚。在这里，我们表明，在与磷脂酰丝氨酸或磷脂酰甘油二聚体结合后，人 2-Cys PrxII (hPrxII) 被组装成三叶形小寡聚体（可能是六聚体），具有完整的分子伴侣和无效的过氧化物酶活性。仅当磷脂酰丝氨酸或磷脂酰甘油与过氧化或 ATP/ADP 结合的 hPrxII 结合时，才会形成球形 HMW 复合物。球形 HMW 复合物是脂质囊泡，覆盖有以六角形格子图案排列的三叶形低聚物。因此，这些带有净负电荷的脂质（可以通过氧化应激下增加的膜运输来提供）对于 hPrxII 以及可能大多数 2-Cys Prxs 的结构和功能转换至关重要。
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.