Thermal Proteome Profiling Chlorotonil derivative in S. aureus USA300
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Fusion
ORGANISM(S): Staphylococcus Aureus
SUBMITTER: 
Dietrich Mostert
LAB HEAD: Stephan Sieber
PROVIDER: PXD051670 | Pride | 2025-03-08
REPOSITORIES: Pride
Dataset's files
Items per page: 5 1 - 5 of 23 |
Similar Datasets
Project description:Thermal Proteome Profiling (TPP) analysis has been applied to a thermophilic bacterial proteome, recently isolated strain of Geobacillus thermoloverans, ARTW1 and thermal stability of more than 1000 proteins were presented. The thermal proteome was investigated in terms of thermostable enzymes that are relevant to industrial applications.
2020-10-14 | PXD018380 | Pride
Project description:We have developed a mass spectrometry-based approach that allowed us to quantitatively monitor protein stability across a broad range of temperatures at the proteome scale (meltome). We profiled the meltomes of several microorganisms and eukaryotic species including human, allowing to investigate the determinants of protein thermostability and survival in various environmental niches. Moreover, we will make Meltome Atlas a valuable, publicly available resource for the biological community to investigate their proteins of interest in the context of protein thermostbility.
2020-04-29 | PXD011929 | Pride
Project description:The cytotoxic and antifungal peptolides vioprolide A-D were discovered in 1996, however their mode-of-action has so far been unsolved. Anti-cancer effect of the most potent cytotoxic derivative vioprolide A (VioA) were evaluated, showing a prominent potency against human acute lymphoblastic leukemia (ALL) cells. In order to decipher the molecular mode-of-action, a VioA-derived photoprobe (VioA-P) was synthesized and utilized for MS-based AfBPP experiments. In addition thermal protein profiling (TPP) experiments with unmodified VioA were conducted for target discovery. TPP experiments revealed a strong thermal stabilization of two proteins after filtering. NOP14, the protein showing the strongest stabilization effect could further be verified as target with continuative biochemical experiments. As various protein-protein interactions with NOP14 are essential in ribosome biogenesis, e.g. with NOC4L and EMG1 for proper maturation of 18S rRNA and 40S assembly and export, the interactome of NOP14 was revealed by MS-based co-Immunoprecipitation. Our findings indicate, that VioA treatment leads to a loss of interaction between NOP14 and EMG1, whereas the NOP14-NOC4L interface remained unperturbed. These findings could be verified independently by western blot, also showing that overall protein expression of NOP14, EMG1 and NOC4L remained unaltered upon VioA treatment. Delocalization of EMG1 from the nucleus into the cytoplasm as consequence of missing interaction with NOP14 could be verified by immunostaining.
2020-01-13 | PXD015196 | Pride
Project description:Urothelial cancer is a challenging disease with a wide tumor-biological spec-trum. Most molecular classification attempts are transcriptome-based and re-late only indirectly to the therapeutically relevant protein level. We improve preanalytical preparation of clinical samples for proteome analyses and char-acterize a comprehensive cohort of 434 samples with 242 tumors and 192 paired normal mucosae. We evaluate sample-wise tumor specificity and rank biomarkers by target relevance. We identify five tumor clusters that add prog-nostic information independent from histopathological groups. In silico drug prediction suggests efficacy of several compounds hitherto not in clinical use. Both, in silico as well as in vitro data, indicate predictive value of the proteo-mic clusters for these drugs. Comparative validation on external transcriptom-ic data confirms prognostic relevance and contextualizes proteomic and tran-scriptomic classifications. A real-world diagnostic approach based on im-munohistochemistry further validates our proteomic data but underlines the necessity of omics scale molecular analyses for personalized oncology.
2024-06-16 | PXD041733 | Pride
Project description:Lagunamide A is a biologically active natural product with a yet unidentified molecular mode of action. Cellular studies revealed that lagunamide A is a potent inhibitor of cancer cell proliferation, promotes apoptosis and causes mitochondrial dysfunction. To decipher the cellular mechanism responsible for these effects, we utilized chemical proteomics and identified EYA3 as a target of lagunamide A. EYA3 was functionally validated via knockout and its role for the anti-proliferative and pro-apoptotic effects of lagunamide A was confirmed. As EYA3 turned out to be important for DNA damage repair, we showed that lagunamide A sensitized tumor cells to treatment with the drug doxorubicin highlighting a putative therapeutic strategy.
2024-06-09 | PXD042129 | Pride
Project description:Transcriptional profiling of probiotic Lactobacillus rhamnosus strain GG mid-exponential pH-controlled bioreactor cultures before and after exposure to bovine bile (0.2% ox gall). Keywords: bile, stress response Cell samples from four biological replicates were harvested right before (time point 0 min) and 10, 30 and 120 min after bile treatment. Each sample was compared to a common reference sample (time point 0 min, mid-exponential growth phase Lactobacillus rhamnosus GG cultures). A total of 12 hybridizations were performed using balanced dye-swap design. Dyes were balanced between compared sample pairs and between biological replicates.
2011-01-01 | E-GEOD-22536 | biostudies-arrayexpress
Project description:Despite having exquisite control over nanoparticle design, controlling nanoparticle fate in vivo remains a major barrier for clinical translation. This is because we do not understand how nanoparticles interact with the surrounding environment in vivo and how this lack of control contributes towards organ accumulation. The suggested link between nanoparticle interactions and organ accumulation are the proteins that adsorb to the nanoparticle surface following administration. How this network of proteins changes during nanoparticle transport, and its influence over the fate of where nanoparticles distribute inside of the body is fundamentally not understood. Here we developed a simple workflow to show that the evolution of proteins on the surface of nanoparticles predicts the biological fate of nanoparticles in vivo. This workflow involves extracting nanoparticles at multiple time points from circulation, isolating the proteins off the surface, and training a neural network to predict nanoparticle biological fate using the proteins as inputs and clearance and organ accumulation as outputs. In a double-blind study, we validated the model by predicting nanoparticle clearance and spleen and liver accumulation with 76-97% accuracy. This work demonstrates that a link between surface adsorbed proteins and the biological fate of nanomaterials exists, and that it can be predicted using the workflow we designed. As we acquire more training data, the strength of these relationships will become more powerful. With more training data we will use more sophisticated neural networks to identify proteins and pathways to target, or create more effective nanomaterial designs to improve clinical translation.
2024-09-14 | PXD011354 | Pride
Project description:Staphylococcus aureus represents an opportunistic pathogen which utilizes elaborate quorum sensing mechanisms to precisely control the expression and secretion of virulence factors. Previous studies indicated a role of the ClpXP proteolytic system in controlling pathogenesis. While detailed transcriptome data for ClpP and ClpX is available, corresponding studies on the proteome, secretome and metabolome level are largely lacking. In order to decipher the functional roles of ClpP and ClpX more globally we utilized S. aureus deletion mutants of the corresponding genes for in-depth proteomic LC-MS/MS analysis. These studies were complemented by a ClpP active site mutant strain to monitor changes solely depending on the presence and not the activity of the protein. A comparison of these strains with wild type revealed e.g. downregulation of virulence, purine/pyrimidine biosynthesis, iron uptake and stress response. Correspondingly, a reduction of a subset of purine and pyrimidine metabolite levels independently confirmed these results. Interestingly, comparison between the ClpP knockout and ClpP active site mutant strains revealed characteristic differences in UMP biosynthesis and the staphyloferrin B pathway, suggesting that the presence of the protein, although inactive, is important for maintaining these processes. These results are not only of fundamental importance to understand the cellular role of ClpXP but also have implications for the development of novel virulence inhibitor classes.
2021-03-12 | PXD018932 | Pride
Project description:Cysteine thiols of many cancer-associated proteins are attractive targets of anti-cancer agents. Herein, we unequivocally demonstrate a distinct thiol-targeting property of gold(III) mesoporphyrin IX dimethyl ester (AuMesoIX) and its anti-cancer activities. While the binding of cysteine thiols with metal complexes usually occurs via M–S bond formation, AuMesoIX is unique in that the meso-carbon atom of the porphyrin ring is activated by the gold(III) ion to undergo nucleophilic aromatic substitution with thiols. AuMesoIX was shown to modify reactive cysteine residues and inhibit the activities of anti-cancer protein targets including thioredoxin, peroxiredoxin, and deubiquitinases. Treatment of cancer cells with AuMesoIX resulted in the formation of gold-bound sulfur-rich protein aggregates, oxidative stress-mediated cytotoxicity, and accumulation of ubiquitinated proteins. Importantly, AuMesoIX exhibited effective anti-tumor activity in mice. Our study has uncovered a gold(III)-induced ligand scaffold reactivity for thiol targeting that can be exploited for anti-cancer applications.
2021-09-08 | PXD016875 | Pride
Project description:TFIID is a central player in activated transcription initiation. Recent evidence suggests that the role and composition of TFIID is more diverse than previously understood. To investigate the effects of changing the composition of TFIID in a simple system we depleted TAF1 from Drosophila cells and determined the consequences on metal induced transcription at an inducible gene, Metallothionein B (MtnB). We observe a marked increase in the levels of both the mature message and pre-mRNA in TAF1 depleted cells. Under conditions of continued metal exposure, we show that TAF1 depletion increases the magnitude of the initial transcription burst, but has no effect on the timing of that burst. We also show that TAF1 depletion causes delay in the shut-off of transcription upon removal of the stimulus. Thus TAFs are involved in both establishing an upper limit of transcription during induction and efficiently turning the gene off once the inducer is removed. Using genomewide nascent-seq we identify hundreds of genes that are controlled in a similar manner indicating that the findings at this inducible gene are likely generalizable to a large set of promoters. There is a long-standing appreciation for the importance of the spatial and temporal control of transcription. Here we uncover an important third dimension of control, the magnitude of the response. Our results show that the magnitude of the transcriptional response to the same signaling event, even at the same promoter, can vary greatly depending on the composition of the TFIID complex in the cell. Nascent RNA was sequenced from replicate samples of Drosophila S2 cells treated with double-stranded RNA directed against E. coli LacI (Control) or against Drosophlia TAF1 (experimental). Reads per kilo-base per million (RPKM) was determined for each gene and the control and experimental samples were compared to determine the genes that were affected by the depletion of TAF1.
2013-05-01 | E-GEOD-45873 | biostudies-arrayexpress