Within a cell, protein-bound methionines can be chemically or enzymatically oxidized, and subsequently reduced by methionine sulfoxide reductases (Msrs). Methionine oxidation can result in structural damage or be the basis of functional regulation of enzymes. In addition to participating in redox reactions, methionines play an important role as the initiator residue of translated proteins where they are commonly modified at their α-amine group by formylation or acetylation. Here, we investigated how formylation and acetylation of initiator methionines impact their propensity for oxidation and reduction. We show that in vitro, N-terminal methionine residues are particularly prone to chemical oxidation and that their modification by formylation or acetylation greatly enhances their subsequent enzymatic reduction by MsrA and MsrB. Concordantly, in vivo ablation of methionyl-tRNA formyltransferase (MTF) in Escherichia coli increases the prevalence of oxidized methionines within synthesized proteins. We show that oxidation of formylated initiator methionines is detrimental in part because it obstructs their ensuing deformylation by peptide deformylase (PDF) and hydrolysis by methionyl aminopeptidase (MAP). Thus, by facilitating their reduction, formylation mitigates the misprocessing of oxidized initiator methionines.

中文翻译：

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甲酰化有助于氧化引发剂蛋氨酸的还原


在细胞内，蛋白质结合的蛋氨酸可以被化学或酶促氧化，随后被蛋氨酸亚砜还原酶 （Msrs） 还原。蛋氨酸氧化可导致结构损伤或成为酶功能调节的基础。除了参与氧化还原反应外，蛋氨酸作为翻译蛋白的起始残基还起着重要作用，它们通常通过甲酰化或乙酰化在其 α-胺基团处进行修饰。在这里，我们研究了引发剂蛋氨酸的甲酰化和乙酰化如何影响它们的氧化和还原倾向。我们表明，在体外，N 末端蛋氨酸残基特别容易发生化学氧化，并且它们通过甲酰化或乙酰化的修饰大大增强了它们随后被 MsrA 和 MsrB 酶促还原。一致地，大肠杆菌中甲硫氨酸-tRNA 甲酰转移酶 （MTF） 的体内消融增加了合成蛋白质中氧化蛋氨酸的普遍性。我们表明，甲酰化引发剂蛋氨酸的氧化是有害的，部分原因是它阻碍了它们随后被肽变形酶 （PDF） 和甲硫氨酰氨肽酶 （MAP） 水解。因此，通过促进它们的还原，甲酰化减轻了氧化引发剂蛋氨酸的错误加工。