Trans-editing of mischarged tRNAs
Trans-editing of mischarged tRNAs
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DOI：
10.1073/pnas.2136934100
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发表时间：
2003-12-23
影响因子：
11.1
通讯作者：
Söll, D
中科院分区：
文献类型：
--
作者：
Ahel, I;Korencic, D;Söll, D
氨基酰基trna合成酶（aars）是一种多结构域蛋白，能够将氨基酸特异地连接到其同源trna上。它们最保守，也可能是进化上最古老的结构域是催化核，它激活氨基酸并将它们转移到trna的3'端。附加或插入到aars体内的额外结构域通过提供额外的tRNA接触或水解非同源氨基酸产物（顺式编辑）来提高氨基酰化过程的效率和特异性。在这里，我们报道了特异的trna依赖的aars样蛋白的反式编辑，这些蛋白相互作用于aars的编辑结构域，而不是相应酶的其余部分。来自sticklandii梭状芽胞杆菌的PrdX蛋白是脯氨酸- trna合成酶编辑域的独立同源物，能高效特异地水解Ala-tRNAPro。同样，来自Methanosarcina barkeri和Sulfolobus solfataricus的自主alanyl-tRNA合成酶编辑结构域同源物（AlaX蛋白）可水解Ser-tRNA（Ala）和Gly-tRNA（Ala）底物。有效水解错酰化产物的自主编辑蛋白的发现，在仅由催化核心组成的祖先aars和附加功能独立模块的现存酶之间提供了直接联系。
Aminoacyl-tRNA synthetases (aaRSs) are multidomain proteins that specifically attach amino acids to their cognate tRNAs. Their most conserved, and presumably evolutionarily oldest, domains are the catalytic cores, which activate amino acids and transfer them to the 3' ends of tRNAs. Additional domains appended to or inserted in the body of aaRSs increase efficiency and specificity of the aminoacylation process, either by providing additional tRNA contacts, or by hydrolyzing noncognate amino acid products (cis-editing). Here, we report specific tRNA-dependent trans-editing by aaRS-like proteins that reciprocate the editing domains of aaRSs, but not the remainder of the corresponding enzyme. A freestanding homologue of the prolyl-tRNA synthetase-editing domain, the PrdX protein from Clostridium sticklandii, efficiently and specifically hydrolyzes Ala-tRNAPro. Similarly, autonomous alanyl-tRNA synthetase-editing domain homologues (AlaX proteins) from Methanosarcina barkeri and Sulfolobus solfataricus hydrolyze Ser-tRNA(Ala) and Gly-tRNA(Ala) substrates. The discovery of autonomous editing proteins efficient in hydrolyzing misacylated products provides a direct link between ancestral aaRSs consisting solely of the catalytic core and extant enzymes to which functionally independent modules are appended.