Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PRM analysis of C-glycosylation substrate

ABSTRACT: To assess the impact of mutations on CMT activity C-glycosylation within RNase E was monitored using PRM analysis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Nichollas Scott

LAB HEAD: Ethan D. Goddard-Borger

PROVIDER: PXD032391 | Pride | 2022-11-01

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	.DS_Store	Other
	20211105_NSco-3297_EGB_AJ_A1_CMT.raw	Raw
	20211105_NSco-3297_EGB_AJ_A1_E220A.raw	Raw
	20211105_NSco-3297_EGB_AJ_A1_E220Q.raw	Raw
	20211105_NSco-3297_EGB_AJ_A1_E400Q.raw	Raw

Items per page:

1 - 5 of 129

Similar Datasets

Tryptophan C-mannosylation is critical for Plasmodium falciparum transmission Dataset1

Project description:C-mannosylation stabilizes proteins bearing a thrombospondin repeat (TSR) domain in metazoans. Here we show that Plasmodium falciparum expresses a DPY19 C-mannosyltransferase in the endoplasmic reticulum and that DPY19-deficiency abolishes C-glycosylation, destabilizes members of the TRAP adhesin family and inhibits transmission to mosquitoes. P. falciparum gametogenesis was imaged in its entirety in four dimensions using lattice light-sheet microscopy. This revealed defects in egress and exflagellation for DPY19 microgametes. While exflagellation was diminished, DPY19 microgametes still fertilized macrogametes, forming ookinetes but these were abrogated for mosquito infection. The gametogenesis defects corresponded with destabilization of MTRAP, which we show is C-mannosylated in P. falciparum, and the ookinete defect was concordant with defective CTRP secretion on the DPY19 background. Genetic complementation of DPY19 restored ookinete infectivity, sporozoite production and C-mannosylation activity. Therefore, tryptophan C-mannosylation by DPY19 in the early secretory pathway ensures TSR protein quality control at two lifecycle stages for successful transmission of the human malaria parasite.

2022-07-06 | PXD033470 | Pride

Determination of Gag stoichiometry for different production platforms by PRM analysis

Project description:In this work we established an analytical method of characterization for the Gag protein core and clarify the current variability of Gag stoichiometry in HIV-1 VLPs depending on the cell-based production platform, directly determining the number of Gag molecules per VLP in each case. Three Gag peptides have been validated to quantify the number of monomers using parallel reaction monitoring (PRM)

2022-12-07 | PXD021278 | Pride

Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase is associated with Charcot-Marie-Tooth neuropathy

Project description:Charcot-Marie-Tooth disease (CMT) is a length-dependent peripheral neuropathy. The aminoacyl-tRNA synthetases constitute the largest protein family implicated in CMT. Aminoacyl-tRNA synthetases are predominantly cytoplasmic, but are also present in the nucleus. Here we show that a nuclear function of tyrosyl-tRNA synthetase (TyrRS) is implicated in a Drosophila model of CMT. CMT-causing mutations in TyrRS induce unique conformational changes, which confer capacity for aberrant interactions with transcriptional regulators in the nucleus, leading to transcription factor E2F1 hyperactivation. Using neuronal tissues, we reveal a broad transcriptional regulation network associated with wild-type TyrRS expression, which is disturbed when a CMT-mutant is expressed. Pharmacological inhibition of TyrRS nuclear entry with embelin reduces, whereas genetic nuclear exclusion of mutant TyrRS prevents hallmark phenotypes of CMT in the Drosophila model. These data highlight that this translation factor may contribute to transcriptional regulation in neurons, and suggest a therapeutic target for CMT.

2019-10-01 | GSE125311 | GEO

Development of gene signatures for doxorubicin resistance and cancer stem cell CD44+, CD24-/low ALD+ isolated from canine mammary adenocarcinoma cell line (microRNA)

Project description:CMT-Stylo is a canine mammary gland adenocarcinoma cell line. From this cell line, a doxorubicin resistant subline called CMT-Star was developed by culturing the cells in the presence of doxorubicin from low concentration to 100 nM doxorubicin (to induce drug resistance). The CMT-Stylo cells were maintained in Dulbecco’s modified eagles medium (DMEM) supplemented with 10% Foetal bovine serum (FBS) and 1% Penicillin-Streptomycin (ThermoFisher Scientific, USA) in 5% CO2 at 370C. The CMT-Star cell line was maintained in additional 5 nM doxorubicin to maintain its resistant phenotype.

2020-12-31 | GSE114889 | GEO

Development of gene signatures for doxorubicin resistance and cancer stem cell CD44+, CD24-/low ALD+ isolated from canine mammary adenocarcinoma cell line (mRNA)

2020-12-31 | GSE114888 | GEO

tRNA overexpression rescues peripheral neuropathy caused by mutations in tRNA synthetase

Project description:Heterozygous mutations in six tRNA synthetase genes cause Charcot-Marie-Tooth (CMT) peripheral neuropathy. CMT-mutant glycyl- or tyrosyl-tRNA synthetases inhibit global protein synthesis by an unknown mechanism, independent of aminoacylation activity. We report that tRNAGly overexpression rescues protein synthesis and peripheral neuropathy phenotypes in Drosophila and mouse models of CMT caused by glycyl-tRNA synthetase (GlyRS) mutations (CMT2D). Kinetic experiments revealed that CMT-mutant GlyRS bind tRNAGly, but display markedly slow release rates. This tRNAGly sequestration may deplete the cellular tRNAGly pool, leading to insufficient glycyl-tRNAGly supply to the ribosome and translation deficit.

2021-09-07 | GSE160584 | GEO

Discovery and characterization of a new class of O-linking oligosaccharyltransferase from bacteria in the Moraxellaceae family

Project description:Bacterial protein glycosylation can be mediated by oligosaccharyltransferases (OTases) that transfer a preassembled lipid-linked oligosaccharide or polysaccharide en bloc to acceptor proteins. O-linking OTases transfer O-antigen or capsular polysaccharides to the side chains of serine or threonine residues. Three major families of bacterial O-linking OTases have been described so far: PglL, PglS, and TfpO. TfpO enzymes are limited to transferring only short glycans whereas there are no clear upper limits for the other two families. Herein, we describe the discovery of a novel family of bacterial O-linking OTases from Moraxellacea bacteria that are similar in size and sequence to TfpO enzymes but can transfer long-chain bacterial glycans to acceptor proteins. Bioinformatic analyses show that these enzymes cluster in different clades than known bacterial OTases. Using a representative enzyme from Moraxella osloensis termed TfpMMo, we determine that the enzyme glycosylates the C-terminal amino acid side chain of a pilin protein and find that pilin fragments as short as three amino acids are substrates for the OTase. The ability of TfpMMo to transfer long-chain polysaccharide shows that this ability is not limited to the PglS and PglL families. TfpMMo is also shown to have broad substrate specificity and can transfer diverse glycans including those with glucose, galactose, or 2-N-acetyl sugars at the reducing end. The glycan substrate promiscuity of TfpMMo could allow this enzyme to be used to produce bacterial glycoconjugate vaccines. The discovery of a new class of O-linking OTase furthers our understanding of the mechanisms that underly glycan specificity by these and other O-linking OTases and enables more comparative studies of this important enzyme family.

2022-10-13 | PXD033468 | Pride

Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice-the short term restoration

Project description:To more directly understand the mechanisms by which CMT reduced 1PAT-induced T1D development, we examined P23 ileal gene expression profile of Non-obese diabetic mice by RNAseq. There 3 treatments C, 1P and CMT, and each treatment has 4 mice.

2021-09-02 | E-MTAB-9981 | biostudies-arrayexpress

A TFEB nuclear export signal integrates amino acid supply and glucose availability

Project description:How cells coordinate the response to fluctuating carbon and nitrogen availability required to maintain effective homeostasis is a key issue. Amino acid limitation that inactivates mTORC1 promotes de-phosphorylation and nuclear translocation of Transcription Factor EB (TFEB), a key transcriptional regulator of lysosome biogenesis and autophagy that is deregulated in cancer and neurodegeneration. Beyond its cytoplasmic sequestration, how TFEB phosphorylation regulates its nuclear-cytoplasmic shuttling, and whether TFEB can coordinate amino acid supply with glucose availability is poorly understood. Here we show that TFEB phosphorylation on S142 primes for GSK3 phosphorylation on S138, and that phosphorylation of both sites but not either alone activates a previously unrecognised nuclear export signal (NES). Importantly, GSK3 is inactivated by AKT in response to mTORC2 signalling triggered by glucose limitation. Remarkably therefore, the TFEB NES integrates carbon (glucose) and nitrogen (amino acid) availability by controlling TFEB flux through a nuclear import-export cycle.

2018-10-18 | PXD009677 | Pride

Ribo-seq of HEK293T overexpressing WT and G240R GARS

Project description:Charcot-Marie-Tooth (CMT) disease can be caused by mutations in Aminoacyl-tRNA-Synthetases, including G240R mutation in Glycyl-tRNA-Synthetase (GARS). Ribo-seq generates snapshots of translating ribosomes on mRNA and therefore allows analysis of ribosome pausing mRNA. Here we performed Ribo-seq on lysates of HEK293T cells overexpressing GARS, WT or G240R, to dissect mechanism of CMT linked with translation. We found that GARS G240R causes pausing of ribosomes with glycine codons in A-site. The effect is specific for 21 nt ribosome-protected fragments, produced by ribosomes with empty A-sites, suggestive of the deficit of charged Glycyl-tRNA in GARS G240R-CMT.

2021-09-14 | E-MTAB-10342 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data