Occurrence of the aminoacyl‐tRNA synthetases in high‐molecular weight complexes correlates with the size of substrate amino acids

Wolfson, Alexey D.; Knight, Rob

doi:10.1016/j.febslet.2005.05.038

Cited by 9 publications

(11 citation statements)

References 49 publications

(52 reference statements)

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“…The LysRS, LeuRS, and ProRS synthetase activities are found in the mammalian MARS (11), and their presence in a single complex is also consistent with predictions based on the physical chemistry of the corresponding substrate amino acids (28). Sequencing of the LeuRS-encoding clone identified an N-terminal fragment as the interacting partner with LysRS.…”

Section: Discussionmentioning

confidence: 51%

Functional Association between Three Archaeal Aminoacyl-tRNA Synthetases

Prætorius-Ibba

Hausmann

Paras

et al. 2007

Journal of Biological Chemistry

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Aminoacyl-tRNA synthetases (aaRSs) are responsible for attaching amino acids to their cognate tRNAs during protein synthesis. In eukaryotes aaRSs are commonly found in multienzyme complexes, although the role of these complexes is still not completely clear. Associations between aaRSs have also been reported in archaea, including a complex between prolyl-(ProRS) and leucyl-tRNA synthetases (LeuRS) in Methanothermobacter thermautotrophicus that enhances tRNA Pro aminoacylation. Yeast two-hybrid screens suggested that lysyl-tRNA synthetase (LysRS) also associates with LeuRS in M. thermautotrophicus. Co-purification experiments confirmed that LeuRS, LysRS, and ProRS associate in cell-free extracts. LeuRS bound LysRS and ProRS with a comparable K D of about 0.3-0.9 M, further supporting the formation of a stable multi-synthetase complex. The steady-state kinetics of aminoacylation by LysRS indicated that LeuRS specifically reduced the K m for tRNA Lys over 3-fold, with no additional change seen upon the addition of ProRS. No significant changes in aminoacylation by LeuRS or ProRS were observed upon the addition of LysRS. These findings, together with earlier data, indicate the existence of a functional complex of three aminoacyl-tRNA synthetases in archaea in which LeuRS improves the catalytic efficiency of tRNA aminoacylation by both LysRS and ProRS.To ensure that the correct amino acid is incorporated into the growing polypeptide chain during protein biosynthesis, the aminoacyl-tRNA synthetases (aaRSs) 2 must attach the correct amino acid to the corresponding tRNA molecule (1). This essential process, in turn, supplies the ribosome with the aminoacyl-tRNAs that are critical for the synthesis of proteins in all cells. The aaRSs can be divided into two groups, class I and II, based on the architecture of the catalytic domain (2-4). Class I aaRSs, which are normally monomeric, attach the aminoacyl group to the 2Ј-OH of the 3Ј terminal nucleotide of the tRNA, whereas class II aaRSs catalyze the addition to the 3Ј-OH of the tRNA and are usually dimeric. In bacteria, the aaRSs normally act alone as free-standing proteins, although in some instances their activities are enhanced by association with other translation factors (5, 6). In eukaryotic organisms, aaRSs are commonly found in multi-enzyme complexes within the cell that are believed to stabilize the interaction between tRNAs and synthetases, thereby increasing the efficiency of aminoacylation. These multi-enzyme complexes vary depending on the specific aaRSs and accessory proteins involved. For example, a complex forms between two synthetases and a non-synthetase protein in Saccharomyces cerevisiae (7), and there is also evidence for functional interactions between seryl-tRNA synthetase and a peroxisomal protein (8) as well as between tyrosyltRNA synthetase and a protein involved in the regulation of cell wall assembly in yeast (9). A complex of valyl-tRNA synthetase and human elongation factor-1H (10) as well as a larger complex consisting of nine aaRS activities...

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Section: Discussionmentioning

confidence: 51%

Functional Association between Three Archaeal Aminoacyl-tRNA Synthetases

Prætorius-Ibba

Hausmann

Paras

et al. 2007

Journal of Biological Chemistry

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“…It is not clear why certain aaRS s exist as a complex while some are in free form. MSC might help in efficient protein synthesis by preventing mixing of charged tRNAs with cellular pool and by increasing local concentration of tRNA near the site of protein synthesis [13]. …”

Section: Introductionmentioning

confidence: 99%

A genomic glimpse of aminoacyl-tRNA synthetases in malaria parasite Plasmodium falciparum

et al. 2009

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BackgroundPlasmodium parasites are causative agents of malaria which affects >500 million people and claims ~2 million lives annually. The completion of Plasmodium genome sequencing and availability of PlasmoDB database has provided a platform for systematic study of parasite genome. Aminoacyl-tRNA synthetases (aaRSs) are pivotal enzymes for protein translation and other vital cellular processes. We report an extensive analysis of the Plasmodium falciparum genome to identify and classify aaRSs in this organism.ResultsUsing various computational and bioinformatics tools, we have identified 37 aaRSs in P. falciparum. Our key observations are: (i) fraction of proteome dedicated to aaRSs in P. falciparum is very high compared to many other organisms; (ii) 23 out of 37 Pf-aaRS sequences contain signal peptides possibly directing them to different cellular organelles; (iii) expression profiles of Pf-aaRSs vary considerably at various life cycle stages of the parasite; (iv) several PfaaRSs posses very unusual domain architectures; (v) phylogenetic analyses reveal evolutionary relatedness of several parasite aaRSs to bacterial and plants aaRSs; (vi) three dimensional structural modelling has provided insights which could be exploited in inhibitor discovery against parasite aaRSs.ConclusionWe have identified 37 Pf-aaRSs based on our bioinformatics analysis. Our data reveal several unique attributes in this protein family. We have annotated all 37 Pf-aaRSs based on predicted localization, phylogenetics, domain architectures and their overall protein expression profiles. The sets of distinct features elaborated in this work will provide a platform for experimental dissection of this family of enzymes, possibly for the discovery of novel drugs against malaria.

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“…Our hypothesis provides an example of functional co-evolution that links the origin of the MARS to the citric acid cycle. This model does not exclude the possibility that other factors also influenced the formation and evolution of the MARS [17]. Moreover, because ARS complexes enhance the efficiency of translation, we speculate that natural selection favors the inclusion of all twenty ARSs in a complex.…”

Section: Discussionmentioning

confidence: 90%

“…Likewise, the substrates of the nine resident ARSs do not fall into a single class, for example, they include both polar and hydrophobic amino acids. A relationship between MARS-bound ARSs and the size of their corresponding amino acids has been suggested, namely, only ARSs corresponding to intermediate-sized amino acids are in the MARS [17]. According to this hypothesis, the binding of aminoacyl-tRNAs corresponding to intermediate-size amino acids to eEF-1A is disfavored thermodynamically, but balanced by MARS-facilitated transfer of aminoacyl-tRNAs to eEF-1A.…”

Section: The Multi-aminoacyl Trna Synthetase Complex (Mars)mentioning

confidence: 99%

Citric acid cycle and the origin of MARS

Eswarappa

Fox

2013

Trends in Biochemical Sciences

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The vertebrate multi-aminoacyl tRNA synthetase complex (MARS) is an assemblage of nine aminoacyl tRNA synthetases (ARSs) and three non-synthetase scaffold proteins, AIMP1 (aminoacyl tRNA synthetase complex-interacting multifunctional protein-1), AIMP2, and AIMP3. The evolutionary origin of the MARS is unclear, as is the significance of the inclusion of only nine of twenty tRNA synthetases. Eight of the nine amino acids corresponding to ARSs of the MARS are derived from two citric acid cycle intermediates, α-ketoglutatrate and oxaloacetate. We propose that the metabolic link with the citric acid cycle, the appearance of scaffolding proteins AIMP2 and AIMP3, and the subsequent disappearance of the glyoxylate cycle, together facilitated the origin of the MARS in a common ancestor of metazoans and choanoflagellates.

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Occurrence of the aminoacyl‐tRNA synthetases in high‐molecular weight complexes correlates with the size of substrate amino acids

Cited by 9 publications

References 49 publications

Functional Association between Three Archaeal Aminoacyl-tRNA Synthetases

Functional Association between Three Archaeal Aminoacyl-tRNA Synthetases

A genomic glimpse of aminoacyl-tRNA synthetases in malaria parasite Plasmodium falciparum

Citric acid cycle and the origin of MARS

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