the enzyme interacts with the apoptosis signal-regulating kinase ASK1, which involves the active sites of the enzymes and inhibits AKS1, the association is mediated and enhanced by glutamine, it is inhibited by Fas ligation, the enzyme inhibits ASK1-induced apoptosis
the enzyme interacts with the apoptosis signal-regulating kinase ASK1, which involves the active sites of the enzymes and inhibits AKS1, the association is mediated and enhanced by glutamine, it is inhibited by Fas ligation, the enzyme inhibits ASK1-induced apoptosis
Atypical OmpR/PhoB subfamily response regulator GlnR of actinomycetes functions as a homodimer, stabilized by the unphosphorylated conserved Asp-focused charge interactions.
heterozygous mutations in GlnRS cause severe brain disorders. Pathological mutations mapping in the N-terminal domain alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. The reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development
in the multisynthetase complex (MSC) subcomplex (RQA1 subcomplex) comprising arginyl-tRNA synthetase (ArgRS), glutaminyl-tRNA synthetase (GlnRS), and the auxiliary factor aminoacyl tRNA synthetase complex-interacting multifunctional protein 1 ((AIMP1)/p43), the N-terminal domain of ArgRS forms a long coiled-coil structure with the N-terminal helix of AIMP1 and anchors the C-terminal core of GlnRS, thereby playing a central role in assembly of the three components. Mutation of AIMP1 destabilizes the N-terminal helix of ArgRS and abrogates its catalytic activity. The MSC complex is comprised of nine different aminoacyl-tRNA synthetases (ARSs) and three accessary proteins. Mutation of the N-terminal helix of ArgRS liberates GlnRS, which is known to control cell death. This ternary RQA1 complex is further anchores to AIMP2/p38 through interaction with AIMP1. Importance of interactions between the N-terminal domains of ArgRS and AIMP1 for the catalytic and noncatalytic activities of ArgRS and for the assembly of the higher-order MSC protein complex. The N-terminal domain of human GlnRS interacts with ArgRS in the MSC, GlnRS is anchored to the complex by the interaction of its C-terminal core with the Hb helix of ArgRS, structure-function analysis, overview. The RQA1 subcomplex also can form a hexameric structure
the enzyme adopts a boomerang-like shaped structure built of 5 domains, domain organization of the intact enzyme and structure of the functionally important N-terminal domain, modeling of overall structure and domain organization of wild-type, full-length enzyme, structure-function analysis, overview
determination of glutamyl/glutaminyl-tRNA synthetase domain sequences in the proteosome of the organism, classification of proteins into homologous groups by determination and validation of Markov clusters of homologous subsequences, MACHOS, for structure-function analysis, method evaluation, overview
in the multisynthetase complex (MSC) subcomplex (RQA1 subcomplex) comprising arginyl-tRNA synthetase (ArgRS), glutaminyl-tRNA synthetase (GlnRS), and the auxiliary factor aminoacyl tRNA synthetase complex-interacting multifunctional protein 1 ((AIMP1)/p43), the N-terminal domain of ArgRS forms a long coiled-coil structure with the N-terminal helix of AIMP1 and anchors the C-terminal core of GlnRS, thereby playing a central role in assembly of the three components. The MSC complex is comprised of nine different aminoacyl-tRNA synthetases (ARSs) and three accessary proteins. This ternary RQA1 complex is further anchores to AIMP2/p38 through interaction with AIMP1. Importance of interactions between the N-terminal domains of ArgRS and AIMP1 for the assembly of the higher-order MSC protein complex. The N-terminal domain of human GlnRS interacts with ArgRS in the MSC, GlnRS is anchored to the complex by the interaction of its C-terminal core with the Hb helix of ArgRS, structure-function analysis, overview. ArgRS, GlnRS, and AIMP1 form a 1:1:1 ternary complex in the asymmetric unit, besides a trimeric, the RQA1 subcomplex also can form a hexameric structure
purified recombinant His-tagged wild-type and mutant enzymes, sitting drop vapour diffusion method, apo wild-type GlnRS crystallizes from 0.1 M calcium acetate, 0.1 M Tris, pH 6.0, 12.5% w/v PEG 3350, and 60 mM Gly-Gly-Gly, the Y57H mutant crystallizes from 0.1 M ammonium acetate, 0.1 M Bis-Tris, pH 5.5, and 17% w/v PEG 10 000, and the G45V mutant crystallizes from 0.15 M ammonium acetate, 0.1 M Bis-Tris, pH 5.5, 3% w/v PEG 20 000, and 10 mM EDTA, 16°C, X-ray diffraction strutcure determination and analysis at 2.4 A, 3.3 A, and 2.7 A resolution, respectively
naturally occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutant shows a highly reduced aminoacylation activity, heterozygous mutations
naturally occuring mutation involved in early-onset epileptic encephalopathy (EOEE), heterozygous mutation leading to a deletion of part of the catalytic domain and the entire anticodon-binding domain, a loss-of-function mutant
occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutant shows a highly reduced aminoacylation activity, heterozygous mutations
naturally occuring mutation involved in development of brain disorder, modestly affects the conformation of the N-terminal domain and the stability of GlnRS, the mutant shows reduced activity compared to the wild-type. Gly45 is in the solvent-flexible loop between helices alpha4 and alpha5
naturally occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutation is located in the N-terminal domain required for QARS interaction with proteins in the multisynthetase complex and potentially with glutamine tRNA, the mutant shows an over 10fold reduction in aminoacylation activity, heterozygous mutation
naturally occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutation renders QARS less soluble and disrupts the domain structure and overall folding of QARS, the mutant shows no aminoacylation activity in vitro, heterozygous mutation
naturally occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutation renders QARS less soluble, the mutation disrupts QARS-RARS (arginyl-tRNA synthetase 1) interaction and disrupts the domain structure and overall folding of QARS, the mutant shows no aminoacylation activity in vitro, heterozygous mutation
naturally occuring mutation involved in development of brain disorder, modestly affects the conformation of the N-terminal domain and the stability of GlnRS, the mutant shows reduced activity compared to the wild-type. Tyr57 is in the middle of helix alpha5
naturally occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutation is located in the N-terminal domain required for QARS interaction with proteins in the multisynthetase complex and potentially with glutamine tRNA, the mutant shows an over 10fold reduction in aminoacylation activity, heterozygous mutation
a deletion mutant comprising only the C-terminal catalytic domain is targeted into the multienzyme complex, while a deletion mutant comprising only the N-terminal domain is not
the melting curves of mutant enzymes G45V and Y57H comprise two peaks indicating that these mutants unfold along a more complex trajectory. The (un)folding events occur at 46.5°C and 52°C in G45V, and at 46°C and 51°C in Y57H
the melting curves of mutant enzymes G45V and Y57H comprise two peaks indicating that these mutants unfold along a more complex trajectory. The (un)folding events occur at 46.5°C and 52°C in G45V, and at 46°C and 51°C in Y57H
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain Rosetta (DE3)pLysS by nickel affinity chromatography and gel filtration
Fu, Y.; Kim, Y.; Jin, K.S.; Kim, H.S.; Kim, J.H.; Wang, D.; Park, M.; Jo, C.H.; Kwon, N.H.; Kim, D.; Kim, M.H.; Jeon, Y.H.; Hwang, K.Y.; Kim, S.; Cho, Y.
Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for mammalian translation