Evidence against Stable Protein S-Nitrosylation as a Widespread Mechanism of Post-translational Regulation.
Evidence against Stable Protein S-Nitrosylation as a Widespread Mechanism of Post-translational Regulation.
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DOI：
10.1016/j.molcel.2017.12.019
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发表时间：
2018-02-01
期刊：
影响因子：
16
通讯作者：
Eaton P
中科院分区：
文献类型：
--
作者：
Wolhuter K;Whitwell HJ;Switzer CH;Burgoyne JR;Timms JF;Eaton P
S-亚硝化，通常被称为S-亚硝基化，被广泛认为是一种普遍存在的，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-亚硝基键固有的不稳定性不相容，特别是其与硫醇快速反应产生二硫键的倾向。正如预期的那样，我们观察到强大的和广泛的蛋白质S-亚硝化暴露细胞后，亚硝基半胱氨酸或脂多糖。使用抗坏血酸依赖性生物素开关方法检测的蛋白质通常被解释为直接由S-亚硝化调节。然而，这些S-亚硝化蛋白质主要包括导致二硫键形成的瞬时中间体。这些二硫化物很可能是由亚硝化细胞一氧化氮物种升高引起的主要末端效应物。我们建议，S-亚硝化主要作为一个短暂的中间体，导致二硫化物的形成。总的来说，我们的结论是，目前广泛持有的看法，稳定的S-亚硝化直接调节许多蛋白质的功能是显着不正确的。蛋白质S-亚硝化通常被认为是一种稳定的调节性修饰然而，S-亚硝基硫醇是不稳定的，并迅速与硫醇反应形成二硫化物。这里二硫化物被证明是亚硝化信号传导的主要末端效应物蛋白质S-亚硝化作为调节性末端效应物可能会发生，但这可能是罕见的一氧化氮相关分子后修饰蛋白质硫醇，导致功能变化。这种S-亚硝基硫醇被广泛认为是调节性末端效应物修饰。然而，Wolhuter et al.表明S-亚硝化主要作为二硫键形成的瞬时中间体。这进一步加深了我们对一氧化氮如何调节信号传导的理解。
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. Protein S-nitrosation is commonly regarded as a stable, regulatory modification However, S-nitrosothiols are labile and rapidly react with thiols to form disulfides Here disulfides are shown to be the dominant end effectors of nitrosative signaling Protein S-nitrosation as a regulatory end effector may occur, but this may be rare Nitric oxide-related molecules post-translationally modify protein thiols, resulting in functional changes. Such S-nitrosothiols are widely thought to be regulatory end effector modifications. However, Wolhuter et al. show that S-nitrosation predominantly serves as a transient intermediate in the formation of disulfide bonds. This furthers our understanding of how nitric oxide regulates signaling.
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DOI：
10.1083/jcb.200104008
发表时间：
2001-09-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mannick JB;Schonhoff C;Papeta N;Ghafourifar P;Szibor M;Fang K;Gaston B
通讯作者：
Gaston B
影响因子：
3.9
作者：
ARNELLE, DR;STAMLER, JS
通讯作者：
STAMLER, JS
影响因子：
4.8
作者：
Lee, SR;Yang, KS;Rhee, SG
通讯作者：
Rhee, SG
影响因子：
64.5
作者：
Hausladen, A;Privalle, CT;Stamler, JS
通讯作者：
Stamler, JS
影响因子：
64.8
作者：
Jia, L;Bonaventura, C;Stamler, JS
通讯作者：
Stamler, JS