Disease relevance of YARS

• 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 [1].
• 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 tRNATyr, and vice versa, supporting the original hypothesis [1].
• We have established the minimum number of nucleotides from the 3' end of the brome mosaic virus and broad bean mottle virus RNAs required for the formation of structures recognized by the tyrosyl-tRNA synthetase and/or the tRNA nucleotidyltransferase [2].
• METHODS: Freshly isolated or primary cultured human NK cells, as well as the human NK cell line YTS, were transduced with replication-incompetent human immunodeficiency virus (HIV)-based lentiviral vector bearing a GFP reporter gene or a gene of interest under the control of the elongation factor 1alpha (EF1alpha) promoter [3].
• Three patients are free of disease and one patient with a high grade tumor is alive with liver metastases at 2 yars postoperatively [4].

High impact information on YARS

• Here we identify two heterozygous missense mutations (G41R and E196K) and one de novo deletion (153-156delVKQV) in tyrosyl-tRNA synthetase (YARS) in three unrelated families affected with DI-CMTC [5].
• Fragments of TyrRS stimulate angiogenesis, whereas those of TrpRS (T2-TrpRS) inhibit angiogenesis [6].
• The tumor natural killer (NK) cell line YTS was used to examine the cytoskeletal rearrangements required for cytolysis [7].
• Whereas the catalytic domains of the human and bacterial enzymes superimpose, the spatial disposition of the anticodon recognition domain relative to the catalytic domain is unique in mini-TyrRS relative to the bacterial orthologs [8].
• Similarity in the hydropathy profile of tyrosyl-t RNA synthetase and the estrogen receptor [9].

Chemical compound and disease context of YARS

• The Class I aminoacyl-tRNA synthetases are characterized by two signature sequence motifs, "HIGH" and "KMSKS." In Bacillus stearothermophilus tyrosyl-tRNA synthetase, the KMSKS motif (230KFGKT234) has been shown to stabilize the transition state for tyrosine activation through interactions with the pyrophosphate moiety of ATP [10].
• This lysine, which is the most highly conserved residue in the class I aminoacyl-tRNA synthetase family, has been shown to interact with the pyrophosphate moiety of the ATP substrate in the Bacillus stearothermophilus tyrosyl-tRNA synthetase [11].

Biological context of YARS

• Human tyrosyl- and tryptophanyl-tRNA synthetases (TyrRS and TrpRS, respectively) link protein synthesis to signal-transduction pathways, including angiogenesis [6].
• Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative cytokine [1].
• In this paper, we demonstrate that intrinsic fluorescence changes can be used to monitor the pre-steady state kinetics of human tyrosyl-tRNA synthetase [12].
• Here mini TyrRS (but not full-length TyrRS) is shown to stimulate chemotaxis of endothelial cells in vitro and stimulate angiogenesis in each of two in vivo animal models [13].
• It is proposed that like endothelial monocyte-activating protein II and the carboxyl-terminal domain of Arc1p, the carboxyl-terminal domain of human tyrosyl-tRNA 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 [1].

Anatomical context of YARS

• Human tyrosyl-tRNA synthetase from mitochondria (mt-TyrRS) presents dual sequence features characteristic of eubacterial and archaeal TyrRSs, especially in the region containing amino acids recognizing the N1-N72 tyrosine identity pair [14].
• In vivo ablation of CD8+ T cells with mAb YTS 169.4 converted cyst resistant B10.BAR12 mice to cyst susceptible [15].
• Here we use mass spectrometry-based proteomic strategy to characterize protein expression in membrane-enriched fractions derived from human NK lymphoma cell line YTS [16].
• This study shows that a short course of treatment with the non-depleting anti-CD4 monoclonal antibody, YTS 177, completely prevents salivary infiltration and reverses ongoing pathology in the salivary gland [17].
• We highlight the expression of CD86 on YTS and its ability to co-stimulate TCR responses of human CD4+ T-cells, providing an unexpected link between innate and adaptive immune systems [16].

Associations of YARS with chemical compounds

• In particular, three amino acids that stabilize the transition state for the activation of tyrosine in B. stearothermophilus tyrosyl-tRNA synthetase (Cys-35, His-48, and Lys-233) are not present in the human enzyme [12].
• Recent kinetic studies indicate that potassium functionally compensates for the absence of the second lysine in the human tyrosyl-tRNA synthetase (222KKSSS226) [10].
• These results are consistent with the hypothesis that the KMSSS sequence in human tyrosyl-tRNA synthetase stabilizes the transition state for the tyrosine activation reaction by interacting with the pyrophosphate moiety of ATP [10].
• Catalysis of tyrosyl-adenylate formation by the human tyrosyl-tRNA synthetase [12].
• The induced-expression level of His(6)-tagged human TyrRS was about 24% of total cell proteins under IPTG inducing [18].

Other interactions of YARS

• In particular, adaptations to the anticodon recognition domain of TyrRS cause distinct appended domains in TyrRS and TrpRS to occupy the same 3D space and thus to mask a common surface on each synthetase [19].
• The angiogenic activity of mini TyrRS can be opposed by anti-angiogenic chemokines like IP-10 [13].
• One of the TyrRS fragments (mini TyrRS) contains features identical to those in CXC chemokines (like interleukin-8) that also act as angiogenic factors [13].
• Eukaryote proteins other than human TyrRS that have EMAP II-like domains have variants of the heptapeptide motif [20].
• Conformational Flexibility of Cytokine-Like C-Module of Tyrosyl-tRNA Synthetase Monitored by Trp144 Intrinsic Fluorescence [21].

Analytical, diagnostic and therapeutic context of YARS

• Fersht and co-workers have applied a linear free energy relation (Brønsted equation) to analyze site-directed mutagenesis experiments involving the enzyme tyrosyl-tRNA synthetase and have suggested that the Brønsted exponent is linearly correlated with the value of the reaction coordinate at the transition state [22].
• Data from 27 boys and 27 girls from YRS I and 48 boys and 22 girls from the YRS II were included, and a total of 139 and 108 measurements of body size and peak VO2 in boys and girls, respectively, were available [23].
• CC chemokine expression by YTS and primary NK cells treated with or without alcohol was analyzed with the real-time RT-PCR and ELISA [24].
• The present manuscript describes a method for cytoskeleton isolation based on capture with magnetic microbeads and its application to the analysis of the NK like cell line, YTS [25].
• Immunofluorescence analysis of YTS cells indicated that a minor component of IQGAP1 was localized at the cell membrane with the remainder diffusely distributed through out the cytoplasm [26].

References