EXISTENCE OF 2 FORMS OF RAT-LIVER ARGINYL-TRANSFER RNA-SYNTHETASE SUGGESTS CHANNELING OF AMINOACYL-TRANSFER RNA FOR PROTEIN-SYNTHESIS
EXISTENCE OF 2 FORMS OF RAT-LIVER ARGINYL-TRANSFER RNA-SYNTHETASE SUGGESTS CHANNELING OF AMINOACYL-TRANSFER RNA FOR PROTEIN-SYNTHESIS
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DOI：
10.1073/pnas.87.10.3665
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发表时间：
1990-05-01
影响因子：
11.1
通讯作者：
DEUTSCHER, MP
中科院分区：
文献类型：
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作者：
SIVARAM, P;DEUTSCHER, MP
精氨酰-tRNA合成酶（精氨酸-tRNA连接酶，EC 6.1.1.19）在哺乳动物细胞提取物中以游离蛋白质（Mr = 60，000）和组分（Mr = 0.0000）的形式存在。72，000）的高分子量氨酰-tRNA合成酶复合物（Mr > 106）。几个证据表明，低分子量游离形式不是复合物结合酶的蛋白水解降解产物，但它在体内预先存在：（i）内源游离形式的大小不同于体外产生的活性蛋白水解片段，（ii）预期增加或减少蛋白水解量的条件不改变酶的两种形式的比率，和（iii）游离形式含有NH 2-末端甲硫氨酸残基。提出了一个模型，提供了一个合理的存在的两种形式的乙酰-tRNA合成酶在细胞中。在该模型中，复合酶提供了用于蛋白质合成的N-乙酰-tRNA，而游离酶提供了用于通过N-乙酰-tRNA：蛋白质N-乙酰转移酶对蛋白质的NH 2-末端精氨酸修饰的N-乙酰-tRNA。后一过程靶向某些蛋白质，通过泛素依赖性蛋白质降解途径去除。修饰反应需要额外的乙酰基-tRNA库，这导致了这样的结论，即用于蛋白质合成（和/或蛋白质修饰）的乙酰基-tRNA被引导并且不可用于其他过程。其他证据支持通道蛋白质合成进行了讨论。
Arginyl-tRNA synthetase (arginine-tRNA ligase, EC 6.1.1.19) is found in extracts of mammalian cells both as a free protein (Mr = 60,000) and as a component (Mr .apprxeq. 72,000) of the high molecular weight aminoacyl-tRNA synthetase complex (Mr > 106). Several pieces of evidence indicate that the low molecular weight free form is not a proteolytic degradation product of the complex-bound enzyme but that it preexists in vivo: (i) the endogenous free form differs in size from the active proteolytic fragment generated in vitro, (ii) conditions expected to increase or decrease the amount of proteolysis do not alter the ratio of the two forms of the enzyme, and (iii) the free form contains an NH2-terminal methionine residue. A model is presented that provides a rationale for the existence of two forms of arginyl-tRNA synthetase in cells. In this model the complexed enzyme supplies arginyl-tRNA for protein synthesis, whereas the free enzyme provides arginyl-tRNA for the NH2-terminal arginine modification of proteins by arginyl-tRNA: protein arginyltransferase. This latter process targets certain proteins for removal by the ubiquintin-dependent protein degradation pathway. The necessity for an additional pool of arginyl-tRNA for the modification reaction leads to the conclusion that the arginyl-tRNA destined for protein synthesis (and/or protein modification) is channeled and unavailable for other processes. Other evidence supporting channeling in protein synthesis is discussed.