Biochemical and Biophysical Research Communications
Breakthroughs and ViewsMolecular network and functional implications of macromolecular tRNA synthetase complex
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Aminoacyl-tRNA synthetase
Specific recognition between ARSs and tRNAs is critical for the precise translation of the genetic code into the protein sequence. In spite of their common function in protein synthesis, ARSs have been diversified in their molecular weight, primary sequence, and quaternary structure. Based on amino acid sequence alignments and structural features, ARSs have been divided into two classes (Table 2) [14], [15], [16]. The class I synthetases are generally monomers or dimers and share two consensus
Complex formation of aminoacyl-tRNA synthetases
ARSs can also be distinguished, based on their property to form a macromolecular complex. A primitive form of these complexes is present in yeast. The yeast ARS complex is composed of glutamyl- (ERS) and methionyl-tRNA synthetases (MRS), and the non-enzyme component called Arc1p which is homologous to mammalian p43 that is also bound to the multi-ARS complex [17]. Due to its relative simplicity, its structural organization and function have been well understood [18]. This complex is stable in
Structural organization of aminoacyl-tRNA synthetase complex
Although the multi-ARS complex has been known for the last two decades, the structural organization and functional significance of this multi-enzyme complex are not yet completely delineated. Mammalian ARSs have extra peptide appendices that are absent in their prokaryotic counterparts. Because prokaryotic ARSs exist as free forms and do not form macromolecular complexes, eukaryotic extra peptide appendices were considered as responsible for the molecular assembly of the enzymes or in other
Multi-functionality of ARS and functional implications for the complex formation of ARSs
Recent evidence showed that the components of the ARS complex participate in various biological processes in addition to protein synthesis (Fig. 3). Human QRS was shown to have an anti-apoptotic function [50]. QRS specifically interacts with the apoptosis signal-regulating kinase 1 (ASK1) in a glutamine-dependent manner and inhibits the ASK1-mediated apoptosis by inhibiting the kinase activity of ASK1. Since Fas-induced ASK1 and c-Jun N-terminal kinase (JNK) activities are inhibited by the
Conclusions and future prospects
Since many of the complex-forming ARSs are active in the free state in vitro, it is clear that the complex formation is not essential for their catalytic activity. In the multi-ARS complex, the aminoacylation reactions that are catalyzed by the component enzymes would proceed in parallel. Considering the size of the substrate tRNAs, a significant traffic jam during the entrance and exit of the substrates and steric hindrance between them are expected within the complex. Also, the mouse
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2022, Cell Chemical BiologyCitation Excerpt :Three additional members show similar shifts, albeit with either a weaker intensity (QARS and YARS) or higher variation (MARS). Together with the aminoacyl tRNA synthase complex-interacting scaffolding subunits AIMP1, AIMP2, and AIMP3, they constitute most of the components of the multi-tRNA synthetase complex (MSC) (Figure S4B) (Han et al., 2003). These proteins showed similar IMPRINTS profiles as well as melt curves (Figure S4C) and likely shift as a complex, which has been previously observed with IMPRINTS-CETSA during S-phase progression of the cell cycle (Dai et al., 2018).
Modulation of Protein-Interaction States through the Cell Cycle
2018, CellCitation Excerpt :Another example of translation-related complexes is the tRNA ligase multisynthetase complex (MSC). MSC in CORUM comprises eight different cytosolic tRNA ligases and three scaffolding subunits (AIMP1, AIMP2, and AIMP3/EEF1E1) (Han et al., 2003). In a cluster plot of CETSA profiles including all the 20 cytosolic tRNA ligases from the Elu_S dataset, seven of the MSC tRNA ligases and the scaffolding subunits clustered together and the eighth subunit (DARS) was just outside this cluster (Figure 6B).
Dysregulation of mRNA translation and energy metabolism in cancer
2018, Advances in Biological RegulationCitation Excerpt :Secondary to peptide-bond formation, eEF2 (EF-G in prokaryotes), facilitates the translocation of the ribosome to free the A-site, whereas uncharged tRNA is transferred to the E-site which requires hydrolysis of another GTP molecule (Stark et al., 2000; Taylor et al., 2007). The tRNA itself is recycled by the amino acyl synthetase complex that requires hydrolysis of ATP to AMP, which is equivalent to two ATP molecules (Han et al., 2003) (Fig. 1). This makes elongation the most energetically demanding step of mRNA translation requiring a total of two ATPs and two GTPs (Ibba and Soll, 1999) (Fig. 1).