The yeast protein Arc1p binds to tRNA and functions as a cofactor for the methionyl- and glutamyl-tRNA synthetases.

Simos, George; Segref, Alexandra; Fasiolo, Franco; Hellmuth, Klaus; Shevchenko, A.; Mann, Matthias; Hurt, Eduard C.

doi:10.1002/j.1460-2075.1996.tb00927.x

Cited by 229 publications

(382 citation statements)

References 43 publications

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“…E. coli GST (25) has the greatest Z-score (14.1), and other proteins including yeast elongation factor EF1B␥ (26), prostaglandin D synthase (27), yeast prion protein Ure2p (28), E. coli stringent starvation A (29), and N-terminal domains from yeast Arc1p and glutamyl-tRNA synthetase (ERS) show Z-scores ranging from 9.9 to 13.9 (30). Arc1p forms a trimeric complex with ERS and MRS in yeast (31). All proteins except Arc1p have a similar two-domain structure like GST, whereas Arc1p lacks a motif corresponding to the N-terminal domain of GST.…”

Section: Resultsmentioning

confidence: 99%

Determination of Three-dimensional Structure and Residues of the Novel Tumor Suppressor AIMP3/p18 Required for the Interaction with ATM

Kim

Park

Choi

et al. 2008

Journal of Biological Chemistry

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Although AIMP3/p18 is normally associated with the multitRNA synthetase complex via its specific interaction with methionyl-tRNA synthetase, it also works as a tumor suppressor by interacting with ATM, the upstream kinase of p53. To understand the molecular interactions of AIMP3 and the mechanisms involved, we determined the crystal structure of AIMP3 at 2.0-Å resolution and identified its potential sites of interaction with ATM. AIMP3 contains two distinct domains linked by a 7-amino acid (Lys 57 -Ser 63 ) peptide, which contains a 3 10 helix. The 56-amino acid N-terminal domain consists of two helices into which three antiparallel ␤ strands are inserted, and the 111-amino acid C-terminal domain contains a bundle of five helices (Thr 64 -Tyr 152 ) followed by a coiled region (Pro 153 -Leu 169 ). Structural analyses revealed homologous proteins such as yeast glutamyl-tRNA synthetase, Arc1p, EF1B␥, and glutathione S-transferase and suggested two potential molecular binding sites. Moreover, mutations at the C-terminal putative binding site abolished the interaction between AIMP3 and ATM and the ability of AIMP3 to activate p53. Thus, this work identified the two potential molecular interaction sites of AIMP3 and determined the residues critical for its tumor-suppressive activity through the interaction with ATM.Although aminoacyl-tRNA synthetases (ARSs) 4 catalyze the ligation of specific amino acids to their cognate tRNAs, they are multifunctional proteins that are involved in the regulation of diverse signal pathways (1). Several ARSs of higher eukaryotes form an intriguing macromolecular protein complex with three non-enzymatic factors, designated AIMPs (ARS-interacting multifunctional proteins), which are also multiply involved in various biological processes. Of these factors, AIMP1/p43 is secreted as a cytokine that functions in immune response (2, 3), angiogenesis (4), and wound-healing processes (5) and also as a hormone that regulates glucose metabolism (6). AIMP2/p38 has been shown to mediate transforming growth factor-␤ signaling for c-Myc down-regulation (7). AIMP3/p18 binds to the multi-ARS complex by specifically interacting with methionyltRNA synthetase (MRS) and is translocated to the nucleus to activate p53 through the interaction with kinases such as ATM (ataxia telangiectasia mutated) and ATR (ATM-and Rad3-related) in response to DNA damage (8) or oncogenic stress (9). To understand the multifunctionality and regulation of the components of the multi-ARS complex, it is important to determine the three-dimensional structures of the components as well as the whole complex. So far, only the three-dimensional structures of the partial domains of the complex-forming ARSs such as glutamylprolyl-tRNA synthetase (10, 11), aspartyltRNA synthetase (12), and AIMP1/p43 (13, 14) have been elucidated. Here, we report the crystal structure of full-length AIMP3 and the residues and location required for the interaction with ATM. EXPERIMENTAL PROCEDURESCloning, Expression, and Purification of Human AIMP3-The cDN...

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Section: Resultsmentioning

confidence: 99%

Determination of Three-dimensional Structure and Residues of the Novel Tumor Suppressor AIMP3/p18 Required for the Interaction with ATM

Kim

Park

Choi

et al. 2008

Journal of Biological Chemistry

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“…13 For western blots, peroxidase anti-peroxidase (DakoCytomation) and anti-Arc1 (polyclonal, rabbit; E. Hurt; 22 ) were used.…”

Section: Western Blottingmentioning

confidence: 99%

Kar9 controls the nucleocytoplasmic distribution of yeast EB1

Schweiggert

Panigada

Tan³

et al. 2016

Cell Cycle

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The precise temporal and spatial concentration of microtubule-associated proteins (MAPs) within the cell is fundamental to ensure chromosome segregation and correct spindle positioning. MAPs form an intricate web of interactions among each other and compete for binding sites on microtubules. Therefore, when assessing cellular phenotypes upon MAP up-or downregulation, it is important to consider the protein interaction network between individual MAPs. Here, we show that changes in the amounts of the spindle positioning factor Kar9 specifically affect the distribution of yeast EB1 on spindle microtubules, without influencing other microtubule-associated interacting partners of Kar9, i.e. yeast XMAP215 and CLIP-170. Alterations in the distribution of yeast EB1 explain chromosome segregation defects upon knockout, overexpression or stabilization of Kar9 and provide an example for non-linear effects on MAP behavior after perturbation of their equilibrium.

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“…To test this hypothesis, we have sequenced the cDNA for human tyrosyl-tRNA synthetase and expressed the recombinant protein in Escherichia coli cells. During the course of these investigations, it was discovered that the human tyrosyltRNA synthetase consists of three distinct domains, an aminoterminal Rossmann fold domain, an anticodon recognition domain, and an idiosyncratic carboxyl-terminal domain whose amino acid sequence is 49% identical to the putative human cytokine endothelial monocyte-activating protein II (EMAP II), 1 50% identical to the carboxyl-terminal domain of methionyl-tRNA synthetase from Caenorhabditis elegans, and 43% identical to the Arc1p protein (also known as G4p1), which has been postulated to direct tRNA to active sites of the methionyland glutamyl-tRNA synthetases in Saccharomyces cerevisiae (22). This is in contrast to all other known tyrosyl-tRNA synthetase sequences, which possess only the first two domains.…”

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confidence: 99%

Human Tyrosyl-tRNA Synthetase Shares Amino Acid Sequence Homology with a Putative Cytokine

Kleeman¹,

Wei²,

Simpson

et al. 1997

Journal of Biological Chemistry

116

102

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To test the hypothesis that tRNA Tyr recognition differs between bacterial and human tyrosyl-tRNA synthetases, we sequenced several clones identified as human tyrosyl-tRNA synthetase cDNAs by the Human Genome Project. We found that human tyrosyl-tRNA synthetase is composed of three domains: 1) an aminoterminal Rossmann fold domain that is responsible for formation of the activated E⅐Tyr-AMP intermediate and is conserved among bacteria, archeae, and eukaryotes; 2) a tRNA anticodon recognition domain that has not been conserved between bacteria and eukaryotes; and 3) a carboxyl-terminal domain that is unique to the human tyrosyl-tRNA synthetase and whose primary structure is 49% identical to the putative human cytokine endothelial monocyte-activating protein II, 50% identical to the carboxyl-terminal domain of methionyl-tRNA synthetase from Caenorhabditis elegans, and 43% identical to the carboxyl-terminal domain of Arc1p from Saccharomyces cerevisiae. The first two domains of the human tyrosyl-tRNA synthetase are 52, 36, and 16% identical to tyrosyl-tRNA synthetases from S. cerevisiae, Methanococcus jannaschii, and Bacillus stearothermophilus, respectively. Nine of fifteen amino acids known to be involved in the formation of the tyrosyl-adenylate complex in B. stearothermophilus are conserved across all of the organisms, whereas amino acids involved in the recognition of tRNA Tyr are not conserved. Kinetic analyses of recombinant human and B. stearothermophilus tyrosyl-tRNA synthetases expressed in Escherichia coli indicate that human tyrosyl-tRNA synthetase aminoacylates human but not B. stearothermophilus tRNA Tyr , and vice versa, supporting the original hypothesis. It is proposed that like endothelial monocyte-activating protein II and the carboxyl-terminal domain of Arc1p, the carboxyl-terminal domain of human tyrosyltRNA synthetase evolved from gene duplication of the carboxyl-terminal domain of methionyl-tRNA synthetase and may direct tRNA to the active site of the enzyme.Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. For most aminoacyl-tRNA synthetases (E), tRNA aminoacylation can be separated into two steps: formation of a stable enzyme-bound aminoacyladenylate intermediate (E⅐AA-AMP, Equation 1), followed by transfer of the amino acid (AA) from the aminoacyl-adenylate intermediate to the 3Ј end of the tRNA substrate (Equation 2).The 20 different aminoacyl-tRNA synthetases fall into two distinct structural classes (1, 2). Class I aminoacyl-tRNA synthetases (of which tyrosyl-tRNA synthetase is a member) are characterized by a structurally well conserved amino-terminal Rossmann fold domain which contains the signature sequences "HIGH" and "KMSKS" (3, 4). In contrast, the carboxyl-terminal domains of class I aminoacyl-tRNA synthetases are structurally diverse suggesting that the primordial aminoacyl-tRNA synthetase consisted solely of the amino-terminal Rossmann fold (5-8). Both x-ray crystallography and site-directed mutagenesis of class I aminoacyl-tRNA synthet...

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The yeast protein Arc1p binds to tRNA and functions as a cofactor for the methionyl- and glutamyl-tRNA synthetases.

Cited by 229 publications

References 43 publications

Determination of Three-dimensional Structure and Residues of the Novel Tumor Suppressor AIMP3/p18 Required for the Interaction with ATM

Determination of Three-dimensional Structure and Residues of the Novel Tumor Suppressor AIMP3/p18 Required for the Interaction with ATM

Kar9 controls the nucleocytoplasmic distribution of yeast EB1

Human Tyrosyl-tRNA Synthetase Shares Amino Acid Sequence Homology with a Putative Cytokine

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