Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, United States.
ACS Chem Biol. 2020 Dec 18;15(12):3073-3085. doi: 10.1021/acschembio.0c00677. Epub 2020 Nov 23.
Arginylation is a protein post-translational modification catalyzed by arginyl-tRNA transferases (ATE1s), which are critical enzymes conserved across all eukaryotes. Arginylation is a key step in the Arg N-degron pathway, a hierarchical cellular signaling pathway that links the ubiquitin-dependent degradation of a protein to the identity of its N-terminal amino acid side chain. The fidelity of ATE1-catalyzed arginylation is imperative, as this post-translational modification regulates several essential biological processes such as cardiovascular maturation, chromosomal segregation, and even the stress response. While the process of ATE1-catalyzed arginylation has been studied in detail at the cellular level, much remains unknown about the structure of this important enzyme, its mechanism of action, and its regulation. In this work, we detail the current state of knowledge on ATE1-catalyzed arginylation, and we discuss both ongoing and future directions that will reveal the structural and mechanistic details of this essential eukaryotic cellular regulator.
精氨酸化是一种由精氨酰-tRNA 转移酶（ATE1s）催化的蛋白质翻译后修饰，它是所有真核生物中保守的关键酶。精氨酸化是 Arg N-降解物途径的关键步骤，Arg N-降解物途径是一种层次化的细胞信号通路，将蛋白质的泛素依赖性降解与蛋白质 N 端氨基酸侧链的身份联系起来。ATE1 催化的精氨酸化的保真度至关重要，因为这种翻译后修饰调节了几个重要的生物学过程，如心血管成熟、染色体分离，甚至应激反应。虽然 ATE1 催化的精氨酸化过程在细胞水平上已经被详细研究，但关于这种重要酶的结构、作用机制及其调控仍然知之甚少。在这项工作中，我们详细介绍了 ATE1 催化的精氨酸化的当前知识状态，并讨论了正在进行的和未来的方向，这些方向将揭示这个重要的真核细胞调节剂的结构和机制细节。
