Site-Specific Proteomic Mapping Identifies Selectively Modified Regulatory Cysteine Residues in Functionally Distinct Protein Networks.
Site-Specific Proteomic Mapping Identifies Selectively Modified Regulatory Cysteine Residues in Functionally Distinct Protein Networks.
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DOI：
10.1016/j.chembiol.2015.06.010
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发表时间：
2015-07-23
影响因子：
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通讯作者：
Ischiropoulos H
中科院分区：
文献类型：
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作者：
Gould NS;Evans P;Martínez-Acedo P;Marino SM;Gladyshev VN;Carroll KS;Ischiropoulos H
S-酰化、S-谷胱甘肽、S-亚硝化和S-亚硫基化是显著的、化学上截然不同的修饰，它们调节蛋白质的功能、氧化还原敏感和运输。虽然这些修饰的生物学意义越来越受到重视，但它们在蛋白质组中的整合仍不清楚。新的基于MS的技术在生理条件下识别了1,319只小鼠肝脏蛋白质中的2,596个主要独特位点。结构分析将修饰定位在独特的、进化保守的蛋白质片段中，在通常注释的功能区域之外。与预期相反，修饰倾向与调节半胱氨酸反应性的生物物理性质无关。然而，体内化学反应的特异性是微调的，四种修饰和定量蛋白质组学之间的名义互补证明了这一点，表明S-亚硝化的减少与S-谷胱甘肽的增加无关。一项全面的调查揭示了生物相关蛋白质网络中的修饰聚集。这些数据为不同的内源性蛋白质网络的出现提供了第一个证据，这些网络通过特定的半胱氨酸修饰经历氧化还原信号。
S-acylation, S-glutathionylation, S-nitrosylation, and S-sulfenylation are prominent, chemically distinct, modifications that regulate protein function, redox-sensing, and trafficking. Although the biological significance of these modifications is increasingly appreciated, their integration in the proteome remain unknown. Novel MS-based technologies identified 2,596 predominately unique sites in 1,319 mouse liver proteins under physiological conditions. Structural analysis localized the modifications in unique, evolutionary conserved protein segments, outside commonly annotated functional regions. Contrary to expectations, propensity for modification did not correlate with biophysical properties that regulate cysteine reactivity. However, the in vivo chemical reactivity is fine-tuned for specificity, demonstrated by the nominal complementation between the four modifications and quantitative proteomics that showed a reduction in S-nitrosylation is not correlated with increased S-glutathionylation. A comprehensive survey uncovered clustering of modifications within biologically related protein networks. The data provide the first evidence for the occurrence of distinct, endogenous protein networks that undergo redox signaling through specific cysteine modifications.