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

Abstract 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.