Swarthmore College, Swarthmore, PA, USA; Children's Hospital of Philadelphia Research Institute and Departments of Pediatrics, The Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania, PA, 19104, USA.
Proteomics Core Facility, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Biomedical Health and Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Redox Biol. 2021 Nov;47:102153. doi: 10.1016/j.redox.2021.102153. Epub 2021 Oct 1.
Protein cysteine residues are essential for protein folding, participate in enzymatic catalysis, and coordinate the binding of metal ions to proteins. Enzymatically catalyzed and redox-dependent post-translational modifications of cysteine residues are also critical for signal transduction and regulation of protein function and localization. S-nitrosylation, the addition of a nitric oxide equivalent to a cysteine residue, is a redox-dependent modification. In this study, we curated and analyzed four different studies that employed various chemoselective platforms coupled to mass spectrometry to precisely identify S-nitrosocysteine residues in mouse heart proteins. Collectively 1974 S-nitrosocysteine residues in 761 proteins were identified and 33.4% were identified in two or more studies. A core of 75 S-nitrosocysteine residues in 44 proteins were identified in all four studies. Bioinformatic analysis of each study indicated a significant enrichment of mitochondrial proteins participating in metabolism. Regulatory proteins in glycolysis, TCA cycle, oxidative phosphorylation and ATP production, long chain fatty acid β-oxidation, and ketone and amino acid metabolism constitute the major functional pathways impacted by protein S-nitrosylation. In the cardiovascular system, nitric oxide signaling regulates vasodilation and cardiac muscle contractility. The meta-analysis of the proteomic data supports the hypothesis that nitric oxide signaling via protein S-nitrosylation is also a regulator of cardiomyocyte metabolism that coordinates fuel utilization to maximize ATP production. As such, protein cysteine S-nitrosylation represents a third functional dimension of nitric oxide signaling in the cardiovascular system to ensure optimal cardiac function.
蛋白质半胱氨酸残基对于蛋白质折叠、参与酶催化以及协调金属离子与蛋白质的结合至关重要。半胱氨酸残基的酶催化和氧化还原依赖性翻译后修饰对于信号转导以及蛋白质功能和定位的调控也至关重要。S-亚硝基化，即一氧化氮等价物添加到半胱氨酸残基上，是一种氧化还原依赖性修饰。在这项研究中，我们整理和分析了四项不同的研究，这些研究采用了各种化学选择性平台与质谱相结合，精确地鉴定了小鼠心脏蛋白质中的 S-亚硝酰半胱氨酸残基。共鉴定出 761 种蛋白质中的 1974 个 S-亚硝酰半胱氨酸残基，其中 33.4%在两项或更多研究中被鉴定出来。在所有四项研究中，有 75 个 S-亚硝酰半胱氨酸残基被鉴定为 44 种蛋白质的核心。对每项研究的生物信息学分析表明，参与代谢的线粒体蛋白质显著富集。糖酵解、三羧酸循环、氧化磷酸化和 ATP 产生、长链脂肪酸 β-氧化以及酮和氨基酸代谢中的调节蛋白构成了受蛋白质 S-亚硝酰化影响的主要功能途径。在心血管系统中，一氧化氮信号调节血管舒张和心肌收缩力。蛋白质组学数据的荟萃分析支持了这样的假设，即通过蛋白质 S-亚硝酰化的一氧化氮信号也是调节心肌细胞代谢的一种机制，它协调燃料利用以最大限度地产生 ATP。因此，蛋白质半胱氨酸 S-亚硝酰化代表了心血管系统中一氧化氮信号的第三个功能维度，以确保最佳的心脏功能。
