The multienzyme complex containing nine aminoacyl-tRNA synthetases is ubiquitous from Drosophila to mammals

Kerjan, Pierre; Cérini, Claire; Sémériva, Michel; Mirande, Marc

doi:10.1016/0304-4165(94)90009-4

Cited by 69 publications

(58 citation statements)

References 16 publications

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“…The complex has been purified to homogeneity from various mammalian tissues, including rat liver, rabbit liver and reticulocytes, sheep liver and spleen Kellermann et al, 1982;Cirakoglu and Waller, 1985;Venema and Traugh, 1991), as well as from cultured cells such as Chinese hamster ovary (CHO) cells (Mirande et al, 1985b) and murine erythroleukemia cells (Norcum, 1989). The complexes purified in these experiments display very similar patterns following gel electrophoresis, comprising 11 polypeptides with molecular weights from 18 kDa to 150 kDa (Kerjan et al, 1992;Kerjan et al, 1994). Although all of the enzymatic activities present can be assigned to their corresponding polypeptides, with the exception of PRS (Mirande et al, 1982;Cirakoglu and Waller, 1985), the structural organization of this complex has not yet been completely deciphered.…”

Section: Mammalian Multi-ars Complexesmentioning

confidence: 82%

Aminoacyl-tRNA synthetase complexes: beyond translation

Lee

Cho

Park

et al. 2004

Journal of Cell Science

221

199

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Although aminoacyl-tRNA synthetases (ARSs) are housekeeping enzymes essential for protein synthesis, they can play non-catalytic roles in diverse biological processes. Some ARSs are capable of forming complexes with each other and additional proteins. This characteristic is most pronounced in mammals, which produce a macromolecular complex comprising nine different ARSs and three additional factors: p43, p38 and p18. We have been aware of the existence of this complex for a long time, but its structure and function have not been well understood. The only apparent distinction between the complex-forming ARSs and those that do not form complexes is their ability to interact with the three non-enzymatic factors. These factors are required not only for the catalytic activity and stability of the associated ARSs, such as isoleucyl-, methionyl-, and arginyl-tRNA synthetase, but also for diverse signal transduction pathways. They may thus have joined the ARS community to coordinate protein synthesis with other biological processes.

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Section: Mammalian Multi-ars Complexesmentioning

confidence: 82%

Aminoacyl-tRNA synthetase complexes: beyond translation

Lee

Cho

Park

et al. 2004

Journal of Cell Science

221

199

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“…Protein solution of LysRS 70 -584 was preincubated with 5 mM L-lysine and 5 mM ATP for 10 min at 22°C. A drop was prepared by mixing 0.1 l of protein solution with 0.1 l of precipitant solution, containing 16% PEG8K, 18% glycerol, 80 mM Na cacodylate (pH 6.05), and 0.16 M Ca(OAc) 2 and was equilibrated against 70 l of precipitant solution. Crystals were collected after incubation at 4°C for 7 days and were flash-frozen at 100 K for data collection.…”

Section: Methodsmentioning

confidence: 99%

“…AIMP2 ͉ aminoacyl-tRNA synthetase ͉ p38 I n higher eukaryotic cells, aminoacyl-tRNA synthetases (AARSs) are organized into a high molecular mass multisynthetase complex (MSC) (1), where at least nine AARSs and three accessory proteins are bound together (2). This complex is not only viable for highly organized protein synthesis (aminoacylation function) (3) but is also thought to serve as a reservoir of regulation molecules for functions beyond aminoacylation.…”

mentioning

confidence: 99%

Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation

Guo

Ignatov

Musier‐Forsyth

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

114

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In mammals, many aminoacyl-tRNA synthetases are bound together in a multisynthetase complex (MSC) as a reservoir of procytokines and regulation molecules for functions beyond aminoacylation. The ␣2 homodimeric lysyl-tRNA synthetase (LysRS) is tightly bound in the MSC and, under specific conditions, is secreted to trigger a proinflammatory response. Results by others suggest that ␣2 LysRS is tightly bound into the core of the MSC with homodimeric ␤2 p38, a scaffolding protein that itself is multifunctional. Not understood is how the two dimeric proteins combine to make a presumptive ␣2␤2 heterotetramer and, in particular, the location of the surfaces on LysRS that would accommodate the p38 interactions. Here we present a 2.3-Å crystal structure of a tetrameric form of human LysRS. The relatively loose (as seen in solution) tetramer interface is assembled from two eukaryotespecific sequences, one in the catalytic-and another in the anticodon-binding domain. This same interface is predicted to provide unique determinants for interaction with p38. The analyses suggest how the core of the MSC is assembled and, more generally, that interactions and functions of synthetases can be built and regulated through dynamic protein-protein interfaces. These interfaces are created from small adaptations to what is otherwise a highly conserved (through evolution) polypeptide sequence.AIMP2 ͉ aminoacyl-tRNA synthetase ͉ p38

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“…hydrophobic) to achieve such an integration (Mirande et al, 1992). A similar complex containing the same nine activities has also been isolated from Drosophila (Kerjan et al, 1994). The largest polypeptide from this complex is a multifunctional enzyme composed of an amino-terminal domain specifying glutamyl-tRNA synthetase activity and of a carboxy-terminal domain specifying prolyl-tRNA synthetase activity.…”

mentioning

confidence: 99%

Evolution of The Aminoacyl‐tRNa Synthetase Family and The Organization of the Drosophila Glutamyl‐Prolyl‐tRNA Synthetase Gene — Intron/Exon Structure of the Gene, Control of Expression of the Two mRNAs, Selective Advantage of the Multienzyme Complex

Cérini

Sémériva

Gratecos

1997

European Journal of Biochemistry

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In Drosophila, glutamyl‐prolyl‐tRNA synthetase is a multifunctional synthetase encoded by a unique gene and composed of three domains: the amino‐ and carboxy‐terminal domains catalyze the aminoacylation of glutamic acid and proline tRNA species, respectively, and the central domain is made of 75 amino acids repeated six times amongst which 46 are highly conserved and constitute the repeated motifs [Cerini, C., Kerjan, P., Astier, M., Gratecos, D., Mirande, M. & Sémériva, M. (1991) EMBO J. 10, 4267–4277]. The intron/exon organization of the Drosophila gene reveals the presence of six exons among which four are in the 5′‐end encoding glutamic acid activity. Only one exon encodes the repeated motifs. A comparison of introns positions, intron classes and intron/exon boundaries in the Drosophila gene and in its human counterpart is compatible with the intron‐early hypothesis presiding, at least in part, to the evolution of the synthetases. The full‐length fly protein is encoded by a 6.1‐kb mRNA which is expressed throughout development. In addition, a shorter transcript encompasses the 3′‐end of the cDNA and it is especially abundant in 5–10‐h embryos until the first larval stage. Expression of these two mRNAs seems to be controlled by two independent promoters. The 6.1‐kb mRNA promoter is probably localized in the 5′‐end of the gene. The small mRNA promoter resides in the 4th intron and evidence is provided that the mRNA encodes only the domain corresponding to prolyl‐tRNA synthetase and is functional in vivo. Finally, transgenic flies have been established by using constructs corresponding to the three domains of the protein. Overexpression of the repeated motifs leads to a sterility of the flies that suggests a role of these motifs in linking the multienzyme complex to an, as yet, unknown structure of the protein synthesis apparatus.

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The multienzyme complex containing nine aminoacyl-tRNA synthetases is ubiquitous from Drosophila to mammals

Cited by 69 publications

References 16 publications

Aminoacyl-tRNA synthetase complexes: beyond translation

Aminoacyl-tRNA synthetase complexes: beyond translation

Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation

Evolution of The Aminoacyl‐tRNa Synthetase Family and The Organization of the Drosophila Glutamyl‐Prolyl‐tRNA Synthetase Gene — Intron/Exon Structure of the Gene, Control of Expression of the Two mRNAs, Selective Advantage of the Multienzyme Complex

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