An archaeal aminoacyl-tRNA synthetase complex for improved substrate quality control.

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 tRNASer recycling through its association with the ribosome. Yet, the way by which complex formation participates in Arg-tRNAArg 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 tRNAArg , providing a rationale for the lack of detectable SerRS•[ArgRS•tRNAArg ] complex. In contrast, stable ternary ArgRS•[SerRS•tRNASer ] complex was easily detected supporting the model wherein ArgRS operates in serylation by modulating SerRS affinity toward tRNASer . We also found that the interaction with SerRS suppresses arginylation of unmodified tRNAArg by ArgRS, which, by itself, does not discriminate against tRNAArg 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.