Seo Taewook, Han Goeun, Cha-Molstad Hyunjoo
Nucleic Acid Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
Department of Biomolecular Science, KRIBB School, University of Science and Technology, Daejeon, Republic of Korea.
Methods Mol Biol. 2023;2620:219-228. doi: 10.1007/978-1-0716-2942-0_24.
Protein arginylation is a unique and under-explored posttranslational modification, which governs many biological functions and the fate of affected proteins. Since ATE1 was discovered in 1963, a central tenet of protein arginylation is that arginylated proteins are destined for proteolysis. However, recent studies have shown that protein arginylation controls not only the half-life of a protein but also various signaling pathways. Here, we introduce a novel molecular tool to elucidate protein arginylation. This new tool, termed R-catcher, is derived from the ZZ domain of p62/sequestosome-1, an N-recognin of the N-degron pathway. The ZZ domain, which has been shown to strongly bind N-terminal arginine, has been modified at specific residues to increase specificity and affinity for N-terminal arginine. R-catcher is a powerful analysis tool allowing researchers to capture the cellular arginylation patterns under various stimuli and conditions, thereby identifying potential therapeutic targets in numerous diseases.
蛋白质精氨酸化是一种独特且尚未充分探索的翻译后修饰，它调控着许多生物学功能以及受影响蛋白质的命运。自1963年发现ATE1以来，蛋白质精氨酸化的一个核心原则是精氨酸化的蛋白质注定会被蛋白酶解。然而，最近的研究表明，蛋白质精氨酸化不仅控制蛋白质的半衰期，还控制各种信号通路。在此，我们介绍一种用于阐明蛋白质精氨酸化的新型分子工具。这种新工具称为R-catcher，它源自p62/聚集体蛋白-1的ZZ结构域，p62/聚集体蛋白-1是N-降解途径的一种N-识别蛋白。已证明ZZ结构域能与N端精氨酸强烈结合，该结构域已在特定残基处进行修饰，以提高对N端精氨酸的特异性和亲和力。R-catcher是一种强大的分析工具，可让研究人员在各种刺激和条件下捕获细胞的精氨酸化模式，从而识别多种疾病中的潜在治疗靶点。
