King's College London, School of Cardiovascular Medicine & Sciences, British Heart Foundation Centre of Research Excellence the Rayne Institute, St. Thomas' Hospital, London SE1 7EH, UK.
Institute for Women's Health, University College London, Gower Street, London WC1E 6BT, UK.
Mol Cell. 2018 Feb 1;69(3):438-450.e5. doi: 10.1016/j.molcel.2017.12.019. Epub 2018 Jan 18.
S-nitrosation, commonly referred to as S-nitrosylation, is widely regarded as a ubiquitous, stable post-translational modification that directly regulates many proteins. Such a widespread role would appear to be incompatible with the inherent lability of the S-nitroso bond, especially its propensity to rapidly react with thiols to generate disulfide bonds. As anticipated, we observed robust and widespread protein S-nitrosation after exposing cells to nitrosocysteine or lipopolysaccharide. Proteins detected using the ascorbate-dependent biotin switch method are typically interpreted to be directly regulated by S-nitrosation. However, these S-nitrosated proteins are shown to predominantly comprise transient intermediates leading to disulfide bond formation. These disulfides are likely to be the dominant end effectors resulting from elevations in nitrosating cellular nitric oxide species. We propose that S-nitrosation primarily serves as a transient intermediate leading to disulfide formation. Overall, we conclude that the current widely held perception that stable S-nitrosation directly regulates the function of many proteins is significantly incorrect.
S-亚硝化作用，通常称为 S-亚硝化，被广泛认为是一种普遍存在且稳定的翻译后修饰，直接调节许多蛋白质。这种广泛的作用似乎与 S-亚硝酰键的固有不稳定性，特别是其与硫醇迅速反应生成二硫键的倾向相矛盾。正如预期的那样，我们在将细胞暴露于亚硝酰半胱氨酸或脂多糖后观察到强烈且广泛的蛋白质 S-亚硝化作用。使用抗坏血酸依赖性生物素开关方法检测到的蛋白质通常被解释为直接受 S-亚硝化作用调节。然而，这些 S-亚硝化的蛋白质主要由导致二硫键形成的瞬时中间体组成。这些二硫键可能是由于细胞中一氧化氮物种的硝化升高而导致的主要终效因子。我们提出 S-亚硝化主要作为导致二硫键形成的瞬时中间体。总的来说，我们得出结论，目前普遍认为稳定的 S-亚硝化直接调节许多蛋白质的功能是显著不正确的。
