Identification of mammalian arginyltransferases that modify a specific subset of protein substrates
Identification of mammalian arginyltransferases that modify a specific subset of protein substrates
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DOI：
10.1073/pnas.0504500102
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发表时间：
2005-07-19
影响因子：
11.1
通讯作者：
Kashina, A
中科院分区：
文献类型：
--
作者：
Rai, R;Kashina, A
由Arg-tRNA-蛋白质转移酶1（ATE 1）介导的翻译后N端蛋白酰化在哺乳动物的心血管发育和血管生成中是必需的，但在酵母中是不必需的。有证据表明，许多蛋白质在哺乳动物和酵母中体内都被乙酰化;然而，在酵母中，N-末端乙酰化只能发生在携带N-末端Asp或Glu的蛋白质上，而在哺乳动物中，N-末端Cys残基也是乙酰化的靶点，这表明Cys乙酰化有助于ATE 1在哺乳动物中的重要作用。到目前为止，所有的特征形式的ATE 1在酵母和哺乳动物已被证明，以乙酰化只有天冬氨酸和谷氨酸，留下开放的猜测是否Cys乙酰化是可能的，只有通过其他组件的哺乳动物乙酰化机制和是否Cys特异性形式的精氨酸转移酶存在于哺乳动物。在这里，我们报告的两种形式的精氨酸转移酶在小鼠中，是特定的N-末端半胱氨酸的鉴定。我们还表明，这两个先前确定的哺乳动物形式的ATE 1可以cystylate含半胱氨酸的基板，除了天冬氨酸和谷氨酸的基板。这一发现提供了深入了解哺乳动物中Cys特异性蛋白酰化的意义，并表明ATE 1分子内底物特异性决定因素的可能性。
Posttranslational N-terminal protein arginylation, mediated by Arg-tRNA-protein transferase 1 (ATE1), is essential for cardiovascular development and angiogenesis in mammals but is nonessential in yeast. Evidence suggests that many proteins are arginylated in vivo in both mammals and yeast; however, in yeast, N-terminal arginylation can occur only on proteins bearing an N-terminal Asp or Glu, whereas in mammals, N-terminal Cys residues are also arginylation targets, suggesting that Cys arginylation contributes to the essential role of ATE1 in mammals. To date, all of the characterized forms of ATE1 in yeast and mammals have been shown to arginylate only Asp and Glu, leaving open to speculation whether Cys arginylation is possible only through other components of mammalian arginylation machinery and whether Cys-specific forms of Arg-transferase exist in mammals. Here, we report the identification of two forms of Arg-transferase in mice that are specific for N-terminal Cys. We also show that the two previously identified mammalian forms of ATE1 can arginylate Cys-containing substrates in addition to Asp- and Glu-containing substrates. This finding provides insights into the significance of Cys-specific protein arginylation in mammals and suggests possibilities of the determinants of substrate specificity within the ATE1 molecule.