The p18 component of the multisynthetase complex shares a protein motif with the β and γ subunits of eukaryotic elongation factor 1

Quevillon, Sophie; Mirande, Marc

doi:10.1016/0014-5793(96)01005-8

Cited by 79 publications

(67 citation statements)

References 27 publications

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“…Another potential ATM coactivator is p18 (AIMP3), which is a component of a translation complex and shows sequence homology to elongation factor subunit (EF-1) (Quevillon and Mirande, 1996), yet appears to function in the DNA damage response. Park et al (2005) showed that p18 regulates ATM-dependent p53 induction after DNA damage, and that ATM and ATR directly interact with p18 after UV and/or adriamycin treatment.…”

Section: Likely Candidates For Inactivators and Activators Of Atmmentioning

confidence: 99%

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

2007

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The ataxia-telangiectasia-mutated (ATM) protein kinase is rapidly and specifically activated in response to DNA double-strand breaks in eukaryotic cells. In this review, we summarize recent insights into the mechanism of ATM activation, focusing on the role of the Mre11/Rad50/Nbs1 (MRN) complex in this process. We also compare observations of the ATM activation process in different biological systems and highlight potential candidates for cellular factors that may participate in regulating ATM activity in human cells.

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Section: Likely Candidates For Inactivators and Activators Of Atmmentioning

confidence: 99%

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

2007

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“…The underlying basis of association has been demonstrated for several of the polypeptides to be the hydrophobic nature of extensions unique to the eukaryotic enzymes (reviewed in Mirande, 1991;Yang, 1996). In addition, specific sequence motifs have been identified in synthetase polypeptides and p l 8 that play a role in proteinprotein interaction (Quevillon & Mirande, 1996;Rho et al, 1996). The overall shape and size of the particle are known from electron microscopy studies (Norcum, 1989).…”

Section: K-rs:p38 D-rs:k-rs R-rs Dimer K-rs Dimer K-rs:q-rs E/p-mentioning

confidence: 99%

Structural analysis of the multienzyme aminoacyl‐tRNA synthetase complex: A three‐domain model based on reversible chemical crosslinking

Norcum

Warrington

1998

Protein Science

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A subset of eukaryotic aminoacyl-tRNA synthetases (a-RS) are contained in a multienzyme complex for which little structural detail is known. Three reversible chemical crosslinking reagents have been used to investigate the arrangement of polypeptides within this particle as isolated from rabbit reticulocytes. Identification of the crosslinked protein pairs was accomplished by two-dimensional SDS diagonal gel electrophoresis. Seventeen neighboring protein pairs have been identified. Eight are seen with at least two reagents: K-RS:p38, D-RS:K-RS, R-RS dimer, K-RS dimer, K-RS:Q-RS, E/P-RS:K-RS, E/P-RS:I-RS, and Q-RS with one of the nonsynthetase proteins. Nine more are observed with one reagent: D-RS dimer, R-RS:p43, D-RS:Q-RS, D-RS:M-RS, K-RS:L-RS, I-RS:R-RS, D-RS:E/P-RS, I-RS:Q-RS, I-RS:L-RS. One trimeric association is seen: E/P-RS:I-RS:L-RS.The observed neighboring protein pairs suggest that the polypeptides within the aminoacyl-tRNA synthetase complex are distributed in three structural domains of similar mass. These can be arranged in a U-shaped particle in which each ''arm'' is considered a domain and the third forms the "base" of the structure. The arms have been termed domain I (D-RS, M-RS, Q-RS) and domain I1 (K-RS, R-RS), with domain III (E/P-RS, I-RS, L-RS) assigned to the base. The smaller proteins (p38, p43) may bridge the domains. This proposed spatial relationship of these domains, as well as their compositions, are consistent with earlier studies. Thus, this study provides an initial three-dimensional working model of the arrangement of polypeptides within the multienzyme aminoacyl-tRNA synthetase complex.Keywords: aminoacyl-tRNA synthetase complex; multienzyme complex; protein-protein interaction; protein structure; reversible chemical crosslinking Aminoacyl-tRNA synthetases are a family of enzymes characterized by their role in coupling each amino acid with the correct tRNA for subsequent use in protein biosynthesis. In addition to this fundamental role in translation, these enzymes are widely studied as models for the evolution of modular proteins and for insight into the mechanisms of RNA-protein recognition. These enzymes also have additional cellular functions, such as synthesis of signaling dinucleotides. There are several recent reviews of these topics (Mirande, 1991;Schulman, 1991;Cusack, 1995).One of the most intriguing and least understood properties of aminoacyl-tRNA synthetases from higher eukaryotes is the existence of a high molecular mass multienzyme complex of a subset Reprint requests to: Mona T. Norcum, Biochemistry Department, University of Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi 39216-4505; e-mail: mnorcum@fiona.umsmed.edu.Abbreviations: a-RS, aminoacyl-tRNA synthetase, a is the one-letter ambo acid abbreviation; cis-DDP, cis-dichlorodiammine platinum; EGS, erhylene glycobis(succinimydy1succinate); SMPT, 4-succinimydyl oxycarbonyl-2-pyridyldithiotoluene. of these proteins (reviewed in Kisselev & Wolfson, 1994;Yang, 1996). As isolated fr...

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“…[1][2][3] The tRNA-binding domain associates with several aminoacyl-tRNA synthetases. On cleavage from the p43 component of the MSC, this domain becomes an independent domain with inflammatory cytokine activity.…”

Section: Introductionmentioning

confidence: 99%

Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration

et al. 2015

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AIMP1/p43 is a multifunctional non-catalytic component of the multisynthetase complex. The complex consists of nine catalytic and three non-catalytic proteins, which catalyze the ligation of amino acids to their cognate tRNA isoacceptors for use in protein translation. To date, two allelic variants in the AIMP1 gene have been reported as the underlying cause of autosomal recessive primary neurodegenerative disorder. Here, we present two consanguineous families from Pakistan and Iran, presenting with moderate to severe intellectual disability, global developmental delay, and speech impairment without neurodegeneration. By the combination of homozygosity mapping and next generation sequencing, we identified two homozygous missense variants, p. (Gly299Arg) and p.(Val176Gly), in the gene AIMP1 that co-segregated with the phenotype in the respective families. Molecular modeling of the variants revealed deleterious effects on the protein structure that are predicted to result in reduced AIMP1 function. Our findings indicate that the clinical spectrum for AIMP1 defects is broader than witnessed so far.

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The p18 component of the multisynthetase complex shares a protein motif with the β and γ subunits of eukaryotic elongation factor 1

Cited by 79 publications

References 27 publications

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

Structural analysis of the multienzyme aminoacyl‐tRNA synthetase complex: A three‐domain model based on reversible chemical crosslinking

Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration

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