State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou, 310024, China.
Cell Mol Life Sci. 2022 Feb 8;79(2):128. doi: 10.1007/s00018-022-04158-9.
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.
氨酰-tRNA 合成酶复合体形成的进化必要性尚不清楚。人赖氨酸-tRNA 合成酶（LysRS）是多 tRNA 合成酶复合体（MSC）的一个组成部分，它不仅对蛋白质翻译至关重要，而且还参与多种细胞途径，如免疫反应、细胞迁移等。在这里，我们结合晶体学、基于 CRISPR/Cas9 的基因组编辑、生物化学和细胞生物学分析，表明来自后生动物的 LysRS 结构比单细胞生物的结构更具动态性。在没有 MSC 支架蛋白（如氨酰-tRNA 合成酶复合体相互作用多功能蛋白 2（AIMP2））的情况下，人 LysRS 游离于 MSC 之外。与 AIMP2 的相互作用稳定了 LysRS 的封闭构象，从而在应激条件下保护必需的氨酰化活性。从人胚肾 293 细胞中删除 AIMP2 会导致在营养缺乏的培养基中细胞生长迟缓。总之，这些结果表明，后生动物中 MSC 的进化出现可能是为了保护氨酰-tRNA 合成酶组件免受修饰或招募用于其他细胞途径。
