Proteolytic signal sequences (PEST) in the mammalian aminoacyl‐tRNA synthetase complex

Jacobo-Molina, Alfredo; Villa-Garcia, Manuel; Chen, Hao-Chia; Yang, David C.H.

doi:10.1016/0014-5793(88)80387-9

Cited by 15 publications

(7 citation statements)

References 20 publications

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“…The fusion of a new domain to an existing protein is a straightforward way to introduce a new function. Indeed, compared with their prokaryotic or lower eukaryotic counterparts, all human AARS (except for AlaRS) have extra domains or motifs at either the N‐ or C‐terminus [5,21,22] (Fig. 1 ).…”

Section: Functional Expansion Through Acquisition Of Extra Domainsmentioning

confidence: 99%

Functional expansion of human tRNA synthetases achieved by structural inventions

2009

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a b s t r a c tKnown as an essential component of the translational apparatus, the aminoacyl-tRNA synthetase family catalyzes the first step reaction in protein synthesis, that is, to specifically attach each amino acid to its cognate tRNA. While preserving this essential role, tRNA synthetases developed other roles during evolution. Human tRNA synthetases, in particular, have diverse functions in different pathways involving angiogenesis, inflammation and apoptosis. The functional diversity is further illustrated in the association with various diseases through genetic mutations that do not affect aminoacylation or protein synthesis. Here we review the accumulated knowledge on how human tRNA synthetases used structural inventions to achieve functional expansions.

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Section: Functional Expansion Through Acquisition Of Extra Domainsmentioning

confidence: 99%

Functional expansion of human tRNA synthetases achieved by structural inventions

2009

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“…As previously observed by electrofocusing analysis of the complex (28), the p43 polypeptide displays a markedly basic pI, evaluated to 9.4 according to its amino acid sequence. The sequences of the three peptides obtained from the p43 component of the sheep complex (Table I) as well as some peptide sequences issued from the rat p43/p38 components (27) were recovered in the protein sequence derived from the cloned cDNA (Fig. 1).…”

Section: Identification Of the Deduced Protein As The P43 Component Omentioning

confidence: 99%

“…The hamster, human, and mouse proteins share only about 60 and 70% of identical residues, respectively for domains III and IV. Domain III has a high serine content (10 Ser, residues 120 -157), whereas domain IV (residues 158 -193) is distinctly hydrophilic, with a stretch of lysine and glutamate Table I determined for the sheep p43 protein are double-underlined; those that were determined for the rat p38/p43 proteins (27) are underlined. The upstream in-frame TGA stop codon, the putative polyadenylation signal, and the poly(A) tract are indicated by a dotted line.…”

Section: Identification Of the Deduced Protein As The P43 Component Omentioning

confidence: 99%

“…The p43 polypeptide was isolated from the complex after denaturation by SDS and fractionation of the 11 polypeptide components by polyacrylamide gel electrophoresis. In the complexes isolated from rat or rabbit, the p43 and p38 components cannot be easily separated (4), leading to cross-contaminating polypeptides (27). Because the p43 component of the sheep complex migrates well apart from the p38 protein, this material was chosen to initiate the cloning process.…”

Section: Isolation Of the Cdna Encoding The P43 Component Of The Multmentioning

confidence: 99%

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The p43 Component of the Mammalian Multi-synthetase Complex Is Likely To Be the Precursor of the Endothelial Monocyte-activating Polypeptide II Cytokine

Quevillon

Agou

Robinson

et al. 1997

Journal of Biological Chemistry

189

190

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p43 is one of the three auxiliary components invariably associated with nine aminoacyl-tRNA synthetases as a multienzyme complex ubiquitous to all eukaryotic cells from flies to humans. The cDNA encoding the hamster protein was isolated by using mixed oligonucleotides deduced from peptide sequences. The 359-amino acid protein is the hamster homologue of the recently reported murine and human EMAP II cytokine implicated in a variety of inflammatory disorders. The sequence of several proEMAP II proteins suggests that the p43 component of the complex is the precursor of the active mature cytokine after cleavage at a conserved Asp residue. The COOH-terminal moiety of p43 is also homologous to polypeptide domains found in bacterial methionyl-or phenylalanyl-tRNA synthetases and in the yeast Arc1p/G4p1 protein that associates with yeast methionyl-tRNA synthetase. Our results implicate the COOH-terminal moiety of p43 as a RNA binding domain. In the native state, as a component of the multisynthetase complex, p43 may be required for tRNA channeling and, after proteolytic processing occurring in tumor cells, would acquire inflammatory properties possibly related to apoptosis. The release of a truncated p43 from the complex could be involved in mediation of the signaling of tumor cells and stimulation of an acute inflammatory response.Aminoacyl-tRNA synthetases catalyze the activation of their cognate amino acid and transfer to the relevant tRNA. In mammals, this family of enzyme contributes two distinct high molecular mass structures: a complex made of nine synthetases and a complex involving valyl-tRNA synthetase and the ␣, ␤, ␥, and ␦ subunits of elongation factor 1. The ten other aminoacyltRNA synthetases are generally described as free enzymes (1-3). The multisynthetase complex contains the nine aminoacyl-tRNA synthetase activities for amino acids Glu, Pro, Ile, Leu, Met, Gln, Lys, Arg, and Asp and the three auxiliary proteins with masses of 18, 38, and 43 kDa. It is ubiquitous to all coelomate metazoan species from arthropods to humans (4). Immunoprecipitation experiments demonstrated the tight association of all of these components (5-7). Electron microscopy studies showed a fairly elongated U-shaped structure (8). Although the three nonsynthetase components were invariably encountered in this complex, their structural or functional role within this multi-subunit structure was not established.We have recently reported the cloning of the cDNA encoding the p18 component of the complex (9). It shares sequence homology with a protein domain recovered in the NH 2 -terminal polypeptide extension of human valyl-tRNA synthetase and in the NH 2 -terminal domains of the ␤ and ␥ subunits of elongation factor 1. In the valyl-tRNA synthetase⅐EF-1H complex, this domain has been involved in protein-protein interaction between the ␤ and ␥ subunits of the eukaryotic elongation factor EF-1H (10) or between valyl-tRNA synthetase and EF-1H (11). This led us to suggest that p18 is involved in anchoring the multisynthetase complex to th...

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“…Aminoacyl-tRNA þ AMP Since bacterial and yeast synthetases occur as free soluble enzymes in cytoplasm under normal conditions, the organization of aaRS's in mammalian cells as a supramolecular assemblage may reveal the evolutionary pressure on the organization of protein biosynthetic machinery [11]. Assessment of the complex and free forms of synthetases indicated that the synthetases complex may provide stabilization against thermal or chemical activation [12] and probably against intracellular proteolysis [13] and to control the synthetase activity. This ubiquitous assembly consists of 11 polypeptide subunits of M r ranging from 18 to 160 kDa which can be purified to homogeneity [14].…”

Section: Introductionmentioning

confidence: 99%

Template-based structure prediction and molecular dynamics simulation study of two mammalian Aspartyl-tRNA synthetases

Ul-Haq

Khan

Zarina

et al. 2010

Journal of Molecular Graphics and Modelling

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Proteolytic signal sequences (PEST) in the mammalian aminoacyl‐tRNA synthetase complex

Cited by 15 publications

References 20 publications

Functional expansion of human tRNA synthetases achieved by structural inventions

Functional expansion of human tRNA synthetases achieved by structural inventions

The p43 Component of the Mammalian Multi-synthetase Complex Is Likely To Be the Precursor of the Endothelial Monocyte-activating Polypeptide II Cytokine

Template-based structure prediction and molecular dynamics simulation study of two mammalian Aspartyl-tRNA synthetases

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