scholarly journals Roles of aminoacyl-tRNA synthetase-interacting multi-functional proteins in physiology and cancer

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Zheng Zhou ◽  
Bao Sun ◽  
Shiqiong Huang ◽  
Dongsheng Yu ◽  
Xiaochuan Zhang
Keyword(s):  
Trna Synthetase ◽  
Scaffold Proteins ◽  
Biological Functions ◽  
Aminoacyl Trna Synthetase ◽  
Exon 2 ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Evolutionarily Conserved ◽  
New Ideas ◽  
Emap Ii

Abstract Aminoacyl-tRNA synthetases (ARSs) are an important class of enzymes with an evolutionarily conserved mechanism for protein synthesis. In higher eukaryotic systems, eight ARSs and three ARS-interacting multi-functional proteins (AIMPs) form a multi-tRNA synthetase complex (MSC), which seems to contribute to cellular homeostasis. Of these, AIMPs are generally considered as non-enzyme factors, playing a scaffolding role during MSC assembly. Although the functions of AIMPs are not fully understood, increasing evidence indicates that these scaffold proteins usually exert tumor-suppressive activities. In addition, endothelial monocyte-activating polypeptide II (EMAP II), as a cleavage product of AIMP1, and AIMP2-DX2, as a splice variant of AIMP2 lacking exon 2, also have a pivotal role in regulating tumorigenesis. In this review, we summarize the biological functions of AIMP1, EMAP II, AIMP2, AIMP2-DX2, and AIMP3. Also, we systematically introduce their emerging roles in cancer, aiming to provide new ideas for the treatment of cancer.

scholarly journals The DRS–AIMP2–EPRS subcomplex acts as a pivot in the multi-tRNA synthetase complex

IUCrJ ◽  
2019 ◽  
Vol 6 (5) ◽  
pp. 958-967 ◽  
Author(s):  
Hyunggu Hahn ◽  
Sang Ho Park ◽  
Hyun-Jung Kim ◽  
Sunghoon Kim ◽  
Byung Woo Han
Keyword(s):  
Hydrogen Bonds ◽  
Synergistic Effects ◽  
Protein Biosynthesis ◽  
Trna Synthetase ◽  
Scaffold Proteins ◽  
Aminoacyl Trna Synthetase ◽  
X Ray ◽  
Trna Synthetases ◽  
Cellular Processes ◽  
Aminoacyl Trna Synthetases

Aminoacyl-tRNA synthetases (ARSs) play essential roles in protein biosynthesis as well as in other cellular processes, often using evolutionarily acquired domains. For possible cooperativity and synergistic effects, nine ARSs assemble into the multi-tRNA synthetase complex (MSC) with three scaffold proteins: aminoacyl-tRNA synthetase complex-interacting multifunctional proteins 1, 2 and 3 (AIMP1, AIMP2 and AIMP3). X-ray crystallographic methods were implemented in order to determine the structure of a ternary subcomplex of the MSC comprising aspartyl-tRNA synthetase (DRS) and two glutathione S-transferase (GST) domains from AIMP2 and glutamyl-prolyl-tRNA synthetase (AIMP2GST and EPRSGST, respectively). While AIMP2GST and EPRSGST interact via conventional GST heterodimerization, DRS strongly interacts with AIMP2GST via hydrogen bonds between the α7–β9 loop of DRS and the β2–α2 loop of AIMP2GST, where Ser156 of AIMP2GST is essential for the assembly. Structural analyses of DRS–AIMP2GST–EPRSGST reveal its pivotal architecture in the MSC and provide valuable insights into the overall assembly and conditionally required disassembly of the MSC.

scholarly journals Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum Time Course

2019 ◽  
Vol 8 (11) ◽  
pp. 2013 ◽  
Author(s):  
Cavagna ◽  
Trallero-Araguás ◽  
Meloni ◽  
Cavazzana ◽  
Rojas-Serrano ◽  
...  
Keyword(s):  
Time Course ◽  
Clinical Presentation ◽  
Reference Group ◽  
Trna Synthetase ◽  
Antisynthetase Syndrome ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Antisynthetase Antibodies ◽  
Clinical Triad

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group’s cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The “ex-novo” occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies’ positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.

scholarly journals The Evolutionary Fate of Mitochondrial Aminoacyl-tRNA Synthetases in Amitochondrial Organisms

2021 ◽  
Author(s):  
Gabor L. Igloi
Keyword(s):  
Protein Sequence ◽  
Identity Element ◽  
Mitochondrial Gene ◽  
Trna Synthetase ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Cognate Trna ◽  
Evolutionary Fate ◽  
Endosymbiotic Evolution

AbstractDuring the endosymbiotic evolution of mitochondria, the genes for aminoacyl-tRNA synthetases were transferred to the ancestral nucleus. A further reduction of mitochondrial function resulted in mitochondrion-related organisms (MRO) with a loss of the organelle genome. The fate of the now redundant ancestral mitochondrial aminoacyl-tRNA synthetase genes is uncertain. The derived protein sequence for arginyl-tRNA synthetase from thirty mitosomal organisms have been classified as originating from the ancestral nuclear or mitochondrial gene and compared to the identity element at position 20 of the cognate tRNA that distinguishes the two enzyme forms. The evolutionary choice between loss and retention of the ancestral mitochondrial gene for arginyl-tRNA synthetase reflects the coevolution of arginyl-tRNA synthetase and tRNA identity elements.

scholarly journals Natural Trojan horse inhibitors of aminoacyl-tRNA synthetases

2021 ◽  
Author(s):  
Dmitrii Y. Travin ◽  
Konstantin Severinov ◽  
Svetlana Dubiley
Keyword(s):  
Trna Synthetase ◽  
Trojan Horse ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Modes Of Action ◽  
Aminoacyl Trna Synthetases

The structures, biosynthesis, and modes of action of albomycin, microcin C and agrocin 84, antibiotics targeting aminoacyl-tRNA synthetases, are reviewed. Using bioinformatics several new putative aminoacyl-tRNA synthetase inhibitors are predicted.

scholarly journals A Novel Aminoacyl-tRNA Synthetase Appended Domain Can Supply the Core Synthetase with Its Amino Acid Substrate

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1320
Author(s):  
Marc Muraski ◽  
Emil Nilsson ◽  
Benjamin Weekley ◽  
Sandhya Bharti Sharma ◽  
Rebecca W. Alexander
Keyword(s):  
Trna Synthetase ◽  
Mycoplasma Species ◽  
Intracellular Pathogen ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Acid Analog ◽  
Methionyl Trna Synthetase ◽  
Acid Substrate ◽  
Amino Acid Substrate

The structural organization and functionality of aminoacyl-tRNA synthetases have been expanded through polypeptide additions to their core aminoacylation domain. We have identified a novel domain appended to the methionyl-tRNA synthetase (MetRS) of the intracellular pathogen Mycoplasma penetrans. Sequence analysis of this N-terminal region suggests the appended domain is an aminotransferase, which we demonstrate here. The aminotransferase domain of MpMetRS is capable of generating methionine from its α-keto acid analog, 2-keto-4-methylthiobutyrate (KMTB). The methionine thus produced can be subsequently attached to cognate tRNAMet in the MpMetRS aminoacylation domain. Genomic erosion in the Mycoplasma species has impaired many canonical biosynthetic pathways, causing them to rely on their host for numerous metabolites. It is still unclear if this bifunctional MetRS is a key part of pathogen life cycle or is a neutral consequence of the reductive evolution experienced by Mycoplasma species.

Molecular Evolution of Aminoacyl tRNA Synthetases and Origin of Universal Genetic Code

1997 ◽  
Vol 161 ◽  
pp. 483-489
Author(s):  
Masahiro Ishigami ◽  
Hideshi Ihara ◽  
Hiroyuki Shinoda
Keyword(s):  
Genetic Code ◽  
Trna Synthetase ◽  
Code System ◽  
Aminoacyl Trna Synthetase ◽  
Synthesis Mechanism ◽  
Primitive Earth ◽  
Universal Genetic Code ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Living Things

AbstractIt is thought that living things first appeared on the primitive earth 35 hundred million years ago. At that time, a primitive protein synthesis mechanism was thought to have been established, a genetic code system evolved, and a universal genetic code system developed. Aminoacyl tRNA synthetase must have evolved with the genetic code system. The aim of the present study is to clarify the evolution of aminoacyl tRNA synthetase and the process and era of the establishment of the universal genetic code system.

Antisynthetase syndrome: A distinct disease spectrum

2020 ◽  
Vol 5 (3) ◽  
pp. 178-191
Author(s):  
Kun Huang ◽  
Rohit Aggarwal
Keyword(s):  
Clinical Characteristics ◽  
Trna Synthetase ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Antisynthetase Syndrome ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Disease Spectrum ◽  
Aminoacyl Trna Synthetases ◽  
Distinct Disease

The discovery of novel autoantibodies related to idiopathic inflammatory myopathies (collectively referred to as myositis) has not only advanced our understanding of the clinical, serological, and pathological correlation in the disease spectrum but also played a role in guiding management and prognosis. One group of the myositis-specific autoantibodies is anti-aminoacyl-tRNA synthetase (anti-ARS or anti-synthetase) which defines a syndrome with predominant interstitial lung disease, arthritis, and myositis. Autoantibodies to eight aminoacyl-tRNA synthetases have been identified with anti-Jo1 the most common in all of idiopathic inflammatory myopathies. Disease presentation and prognosis vary depending on which anti-aminoacyl-tRNA synthetase antibody is present. In this review, we will discuss the clinical characteristics, overlap features with other autoimmune diseases, prognostic factors, and management of the antisynthetase syndrome.

scholarly journals An Archaeal Aminoacyl-tRNA Synthetase Missing from Genomic Analysis

1999 ◽  
Vol 181 (18) ◽  
pp. 5880-5884 ◽  
Author(s):  
Christian S. Hamann ◽  
Kevin R. Sowers ◽  
Richard S. A. Lipman ◽  
Ya-Ming Hou
Keyword(s):  
Protein Synthesis ◽  
Enzyme Activity ◽  
Genomic Analysis ◽  
Trna Synthetase ◽  
Genomic Sequencing ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Cell Lysate ◽  
Aminoacyl Trna Synthetases ◽  
Complete Genomic

ABSTRACT The complete genomic sequencing of Methanococcus jannaschii cannot identify the gene for the cysteine-specific member of aminoacyl-tRNA synthetases. However, we show here that enzyme activity is present in the cell lysate of M. jannaschii. The demonstration of this activity suggests a direct pathway for the synthesis of cysteinyl-tRNACys during protein synthesis.

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