Human lysyl-tRNA synthetase evolves a dynamic structure that can be stabilized by forming complex

The evolutionary necessity of aminoacyl-tRNA synthetases being associated into complex is unknown. Human lysyl-tRNA synthetase (LysRS) is one component of the multi-tRNA synthetase complex (MSC), which is not only critical for protein translation but also involved in multiple cellular pathways such as immune response, cell migration, etc. Here, combined with crystallography, CRISPR/Cas9-based genome editing, biochemistry, and cell biology analyses, we show that the structures of LysRSs from metazoan are more dynamic than those from single-celled organisms. Without the presence of MSC scaffold proteins, such as aminoacyl-tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2), human LysRS is free from the MSC. The interaction with AIMP2 stabilizes the closed conformation of LysRS, thereby protects the essential aminoacylation activity under stressed conditions. Deleting AIMP2 from the human embryonic kidney 293 cells leads to retardation in cell growth in nutrient deficient mediums. Together, these results suggest that the evolutionary emergence of the MSC in metazoan might be to protect the aminoacyl-tRNA synthetase components from being modified or recruited for use in other cellular pathways.

Automated summary

The structures of human Lysyl-tRNA synthetases (LysRSs) are more dynamic than those from single-celled organisms. Without the presence of MSC scaffold proteins, human LysRS can exist independently from the multi-tRNA synthetase complex (MSC). The interaction with the scaffold protein AIMP2 stabilizes the closed conformation of LysRS and protects its essential aminoacylation activity under stressed conditions. Deleting AIMP2 from human cells leads to slow cell growth in nutrient deficient mediums. These results suggest that the evolutionary emergence of the MSC in metazoan might be to protect the aminoacyl-tRNA synthetase components from being modified or recruited for use in other cellular pathways.