Aminoacyl-tRNA synthetases (aaRSs) decode genetic information by coupling tRNAs with cognate amino acids. In the archaeon Methanothermobacter thermautotrophicus arginyl- and seryl-tRNA synthetase (ArgRS and SerRS, respectively) form a complex which enhances serylation and facilitates tRNA^Ser recycling through its association with the ribosome. Yet, the way by which complex formation participates in Arg-tRNA^Arg synthesis is still unresolved. Here we utilized pull down and surface plasmon resonance experiments with truncated ArgRS variants to demonstrate that ArgRS uses its N-terminal domain to establish analogous interactions with both SerRS and cognate tRNA^Arg, providing a rationale for the lack of detectable SerRS•[ArgRS•tRNA^Arg] complex. In contrast, stable ternary ArgRS•[SerRS•tRNA^Ser] complex was easily detected supporting the model wherein ArgRS operates in serylation by modulating SerRS affinity toward tRNA^Ser. We also found that the interaction with SerRS suppresses arginylation of unmodified tRNA^Arg by ArgRS, which, by itself, does not discriminate against tRNA^Arg substrates lacking posttranscriptional modifications. Hence, there is a fundamentally different participation of the protein partners in Arg-tRNA and Ser-tRNA synthesis. Propensity of the ArgRS•SerRS complex to exclude unmodified tRNAs from translation leads to an attractive hypothesis that SerRS•ArgRS complex might act in vivo as a safeguarding switch that improves translation accuracy.

氨酰基-tRNA合成酶（aaRSs）通过将tRNA与同源氨基酸偶联来解码遗传信息。在古细菌甲烷杆菌属嗜热自养菌中，精氨酰和丝氨酰-tRNA合成酶（分别为ArgRS和SerRS）形成一种复合物，该复合物通过与核糖体缔合，增强了Serlation和促进tRNA ^Ser的循环利用。然而，复合物形成参与Arg-tRNA ^Arg合成的方式仍未解决。在这里，我们利用截短的ArgRS变体的下拉和表面等离振子共振实验来证明ArgRS使用其N末端结构域与SerRS和同源tRNA ^Arg建立相似的相互作用，从而为缺乏可检测的SerRS•[ArgRS•tRNA]提供了理论依据^Arg ]复杂。相反，很容易检测到稳定的三元ArgRS•[SerRS•tRNA ^Ser ]复合物，从而支持其中ArgRS通过调节对tRNA ^Ser的SerRS亲和力而在三聚化中起作用的模型。我们还发现，与SerRS的相互作用抑制了ArgRS修饰未修饰的tRNA ^Arg的精氨酰化，而ArgRS本身并不能与缺少转录后修饰的tRNA ^Arg底物区分开。因此，蛋白质伴侣在Arg-tRNA和Ser-tRNA合成中的参与方式根本不同。ArgRS•SerRS复合物从翻译中排除未修饰的tRNA的倾向导致一个有吸引力的假设，即SerRS•ArgRS复合物可能在体内起作用 作为提高翻译准确性的保护开关。