WGS histidine overproducers
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB45772 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Aminoacyl-tRNA synthetases (ARSs) are essential enzymes responsible for charging amino acids onto cognate tRNAs during protein synthesis¬. In histidyl-tRNA synthetase (HARS), autosomal dominant mutations in the HARS catalytic domain are associated with Charcot Marie Tooth Disease Type 2W (CMT2W), while anticodon-binding domain mutations cause Usher Syndrome Type IIIB (USH3B). We use yeast as a model system to study disease-causing HARS mutations (V133F, V155G, Y330C, S356N) associated with CMT2W, and Y454S, associated with USH3B. All human HARS variants complemented genomic deletion of the yeast ortholog HTS1 at high expression levels. CMT2W associated mutations, but not Y454S, result in reduced growth. HARS V155G and S356N cause accumulation of insoluble proteins and mistranslation in yeast, and the growth defect of these mutants was rescued by histidine addition to the growth media, restoring the soluble proteome. V133F and Y330C, on the other hand, lead to decreased HARS abundance. Histidine supplementation further reduced viability in yeast expressing V133F and Y330C, and lead to insoluble protein accumulation, indicating histidine toxicity associated with these mutants. Because histidine is in clinical trials as treatment for USH3B, our data will inform future treatment options for these as well as CMT patients, where histidine supplementation may either have a toxic or compensating effect dependingon the nature of the causative HARS variant.
2023-03-10 | PXD034865 | Pride
Project description:Protein methylation occurs predominantly on lysine and arginine residues, but histidine also serves as a substrate for the modification. However, a limited number of enzymes responsible for this modification have been reported. Moreover, the biological role of histidine methylation has remained poorly understood. Here, we report that human METTL18 is a histidine methyltransferase for the ribosomal protein RPL3 and that the modification specifically slows ribosome traverse on tyrosine codons, allowing the proper folding of synthesized proteins. By performing an in vitro methylation assay with a methyl donor analog and quantitative mass spectrometry, we found that His245 of RPL3 is methylated at the τ-N position by METTL18. Structural comparison of the modified and unmodified ribosomes showed stoichiometric modification and suggested a role in translation tuning. Indeed, genome-wide ribosome profiling revealed suppressed ribosomal translocation at tyrosine codons by RPL3 methylation. Because the slower elongation provides enough time for nascent protein folding, RPL3 methylation protects cells from the cellular aggregation of Tyr-rich proteins. Our results reveal histidine methylation as an example of a “ribosome code” that ensures proteome integrity in cells.
2022-06-15 | GSE200172 | GEO
Project description:For decades, extreme difficulties in analyzing histidine phosphorylation have limited the study of phosphohistidine signaling. Here we report a method revealing widespread and abundant protein histidine phosphorylation in E. coli. Our new approach generated the largest E. coli phosphoproteome dataset to date, of which a remarkable high percentage (~10%) are phosphohistidine sites. This resource enables a major step forward towards a better understanding of the biological function of histidine phosphorylation.
2017-12-07 | PXD008369 | JPOST Repository
Project description:The goal of this experiment is compare gene expression profiles between C. acetobutylicum ATCC 55025, histidine kinase cac3319 and cac0437 inactivated strains to determine the pleiotropic and distinctive functions of histidine kinases on cell differentiation and cellular metabolism. Samples for total RNA extraction were collected from fermentation broth at acidogenic phase (8 h) and solventogenic phase (16 h)
2019-05-01 | E-MTAB-7341 | biostudies-arrayexpress
Project description:A histidine prototrophic strain achieves A600 three-four fold higher than a histidine auxotroph when cultured in nutrient rich media YPA, which is abundant in amino acids. This retaded growth of histidine auxotroph in YPA can also be rescued by supplementing media with exogenous histidine. Here, we aim to study the transcriptomic changes associated with culturing of histidine auxotroph and prototroph in YPA and also the effects of histidine addition to the culture medium of histidine auxotroph.
2022-04-06 | GSE174633 | GEO
Project description:Histidine-rich glycoprotein (HRG) HRG is a liver-produced protein circulating in human plasma serum at high concentrations of around 125 ug/mL. HRG belongs to the family of type-3 cystatins and has been implicated in a plethora of biological processes, albeit its precise function is still not well understood. Human HRG is a highly polymorphic protein, with at least 5 variants with minor allele frequencies (MAF) of more than 10%, variable in populations from different parts of the world. Considering these 5 mutations we can expect already 35 = 243 possible possibly genetic HRG variants in the population. Here, we purified HRG from serum of 44 individual donors and investigated by proteomics the occurrence of different allotypes, each being either homozygote or heterozygote for each of the 5 mutation sites. We observed that some mutational combinations in HRG were highly favored, while others were apparently missing, although they ought to be present based on the stochastic independent assembly of these 5 mutation sites. To further explore this behavior, we extracted data from the 1000 genome project (n ~ 2500 genomes) and assessed the frequency of different HRG mutants in this larger dataset, observing a prevailing agreement with our proteomics data. From all the proteogenomic data we conclude that the 5 different (frequent) mutations sites in HRG are not occurring independently, but some mutational variants at different sites are fully mutually exclusive, whereas other are highly intwined. Specific mutations also affect HRG abundance and its glycosylation. As the levels of HRG have been suggested as a protein biomarker in a variety of biological processes (e.g., aging, COVID-19 severity, severity of bacterial infections), we here conclude that the highly polymorphic nature of the protein needs to be considered in such evaluations, as these mutations affect HRG’s abundance, structure, post-translational modifications, and function.
2023-10-24 | PXD040914 | Pride
Project description:Adenine base editors (ABEs) with wide CRISPR compatibility and high activity improves the editing efficiency and arouses the off-target challenges as well. Here, we carried out a comprehensive evaluation of ABE8e and ABE9 induced DNA and RNA mutations in model organism rice. The whole-genome sequencing analysis on plants with rBE46b (SpCas9n-TadA8e), rBE49b (SpCas9n-TadA9), rBE50 (SpCas9n-NG-TadA8e), rBE53 (SpCas9n-NG-TadA9) reveals that the ABEs with TadA9 lead to a higher number of off-target A>G SNVs and ABEs with SpCas9n-NG lead to a higher total number of off-target SNVs. The analysis of T-DNAs (ABEs carrier) disclosed that the on-target mutations could happen before T-DNA integration to plant genomes as well as after T-DNA integration to plant genomes, while ABEs integrated into plant genomes lead to more A>G SNVs. We also detected off-target A>G RNA mutations in plants with higher expression of ABEs but not in plants with lower expression of ABEs. The off-target A>G RNA mutations tend to cluster while off-target A>G DNA mutations cluster in a very rare manner. The findings that CRISPRs, TadA variants, T-DNA integration, and ABE expression contribute ABEs’ specificity provide alternative ways to increase the specificity of ABEs.
2022-01-01 | GSE185495 | GEO
Project description:Whole-genome sequencing on PacBio of laboratory mouse strains. See http://www.sanger.ac.uk/resources/mouse/genomes/ for more details. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2014-10-15 | E-ERAD-328 | biostudies-arrayexpress
Project description:CTP synthase (CTPS) forms compartmentalized filaments in response to substrate availability and environmental nutrient status. However, the physiological role of filaments and mechanisms for filament assembly are not well understood. Here, we provide evidence that CTPS forms filaments in response to histidine influx during glutamine starvation. CTPS protein levels remained stable in the presence of histidine during nutrient deprivation, followed by rapid cell growth following nutrient replenishment. Tetramer conformation-based filament formation restricted CTPS enzyme activity duringnutrient deprivation. Furthermore, we demonstrated that filament formation controlled at two levels. Starvation stress/glutamine deficiency activates the GCN2/ATF4/MTHFD2 axis to accelerate the folate cycle in mitochondria for energy homeostasis. In addition, histidine promotes re-methylation of homocysteine by donating one-carbon to the cytosolic folate cycle. CTPS filament formation induced by histidine-mediated methylation maybe a strategy usedby cancer cells to maintain homeostasis and ensure a growth advantage in adverse environments.
2018-08-29 | GSE105251 | GEO
Project description:ReeS, previously named as CPE1512, was originally annotated as the only hybrid sensor histidine kinase/response regulator in Clostridium perfringens. Further evidence suggests that ReeS is more likely to function as an orphan sensor histidine kinase. A reeS deletion mutant was constructed and the transcriptome analysed using microarrays.
2013-08-31 | GSE36786 | GEO