The posttranslational methylation of the α-N-terminal amino group of proteins was first documented over 40 years ago, but the functional significance of this modification has been underexplored relative to lysine and arginine methylation. Increasing reports implicates α-N-terminal methylation as a widespread and critical regulator of mitosis, chromatin interactions, DNA repair, and translation fidelity. Here, we summarize advances in the current understanding of protein α-N-terminal methylation biological functions and mechanisms across eukaryotic organisms. Also, we describe the recent literature on substrate recognition and the discovery of potent and selective inhibitors for protein N-terminal methyltransferases. Finally, we summarize the emergent crosstalk between α-N-terminal methylation and other N-terminal modifications.

中文翻译：

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蛋白质 N 端甲基化的过去、现在和展望。

蛋白质的 α-N 末端氨基的翻译后甲基化在 40 多年前首次被记录，但相对于赖氨酸和精氨酸甲基化，这种修饰的功能意义尚未得到充分探索。越来越多的报道表明 α-N 末端甲基化是有丝分裂、染色质相互作用、DNA 修复和翻译保真度的广泛且关键的调节因子。在这里，我们总结了当前对真核生物中蛋白质α-N-末端甲基化生物学功能和机制的理解进展。此外，我们还描述了最近关于底物识别的文献以及发现蛋白质 N 末端甲基转移酶的有效和选择性抑制剂。最后，我们总结了 α-N-末端甲基化和其他 N-末端修饰之间出现的串扰。