S-Nitrosylation of ApoE in Alzheimer's Disease
S-Nitrosylation of ApoE in Alzheimer's Disease
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DOI：
10.1021/bi200266v
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发表时间：
2011-05-03
期刊：
影响因子：
2.9
通讯作者：
Wang, Gaofeng
中科院分区：
文献类型：
--
作者：
Abrams, Alexander J.;Farooq, Amjad;Wang, Gaofeng
载脂蛋白E（ApoE）亚型在功能上影响迟发性阿尔茨海默病（LOAD）的风险和进展的机制至今仍是未知的。在此，我们提供了所有ApoE亚型与一氧化氮合酶1（NOS 1）结合的证据，并且这种蛋白质-蛋白质相互作用导致ApoE 2和ApoE 3而不是ApoE 4的S-亚硝基化。我们在原子水平上的结构分析表明，ApoE 2和ApoE 3蛋白的S-亚硝基化可能导致构象变化，导致与低密度受体结合的丧失。总的来说，我们的数据表明，S-亚硝基化的ApoE蛋白可能在调节脂质代谢和在LOAD的发病机制中发挥重要作用。
The mechanism by which apolipoprotein E (ApoE) isoforms functionally influence the risk and progression of late-onset Alzheimer's disease (LOAD) remains hitherto unknown Herein, we present evidence that all ApoE isoforms bind to nitric oxide synthase 1 (NOS1) and that such protein-protein interaction results in S-nitrosylation of ApoE2 and ApoE3 but not ApoE4. Our structural analysis at the atomic level reveals that S-nitrosylation of ApoE2 and ApoE3 proteins may lead to conformational changes resulting in the loss of binding to low-density receptors. Collectively, our data suggest that S-nitrosylation of ApoE proteins may play an important role in regulating lipid metabolism and in the in the pathogenesis of LOAD.