Protein oxidation: role in signalling and detection by mass spectrometry.
Protein oxidation: role in signalling and detection by mass spectrometry.
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蛋白质氧化：在信号传导和质谱检测中的作用。
DOI：
10.1007/s00726-010-0585-4
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发表时间：
2012
期刊：
影响因子：
3.5
通讯作者：
Spickett CM
中科院分区：
文献类型：
--
作者：
Spickett CM
蛋白质可以经历各种各样的氧化翻译后修饰（oxPTM）;虽然可逆的修饰被认为与生理过程相关，但不可逆的oxPTM可能导致病理情况和疾病。氧化剂在确定oxPTM的类型中也很重要，例如氧化、氯化或硝化。参与信号传导调节的最佳表征的oxPTM是半胱氨酸部分氧化成二硫化物、谷胱甘肽化或次磺酸形式，其可以被硫醇还原剂逆转。脯氨酸羟基化在HIF信号传导中也被很好地表征，并且越来越多的证据表明甲硫氨酸和酪氨酸的特异性氧化可能具有一些生物学作用。对于一些受半胱氨酸氧化调控的蛋白质，所涉及的残基和分子机制已被广泛研究和充分理解，例如蛋白酪氨酸磷酸酶PTP 1B和MAP 3激酶ASK 1，以及转录因子复合物Keap 1-Nrf 2。分析技术的进步，特别是串联质谱技术的进步促进了对oxPTM在信号传导中的作用的理解。通过碰撞诱导解离和前体离子扫描或中性损失来选择特定oxPTM的肽测序的组合已被证明对于鉴定氧化修饰的蛋白质和绘制氧化位点非常有用。S-亚硝基化或二硫化物形成的特定标记和富集程序的开发已被证明是非常宝贵的，并且正在进行的工作是建立用于检测硝基酪氨酸和其他修饰的类似方法。
Proteins can undergo a wide variety of oxidative post-translational modifications (oxPTM); while reversible modifications are thought to be relevant in physiological processes, non-reversible oxPTM may contribute to pathological situations and disease. The oxidant is also important in determining the type of oxPTM, such as oxidation, chlorination or nitration. The best characterized oxPTMs involved in signalling modulation are partial oxidations of cysteine to disulfide, glutathionylated or sulfenic acid forms that can be reversed by thiol reductants. Proline hydroxylation in HIF signalling is also quite well characterized, and there is increasing evidence that specific oxidations of methionine and tyrosine may have some biological roles. For some proteins regulated by cysteine oxidation, the residues and molecular mechanism involved have been extensively studied and are well understood, such as the protein tyrosine phosphatase PTP1B and MAP3 kinase ASK1, as well as transcription factor complex Keap1–Nrf2. The advances in understanding of the role oxPTMs in signalling have been facilitated by advances in analytical technology, in particular tandem mass spectrometry techniques. Combinations of peptide sequencing by collisionally induced dissociation and precursor ion scanning or neutral loss to select for specific oxPTMs have proved very useful for identifying oxidatively modified proteins and mapping the sites of oxidation. The development of specific labelling and enrichment procedures for S-nitrosylation or disulfide formation has proved invaluable, and there is ongoing work to establish analogous methods for detection of nitrotyrosine and other modifications.