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PROMIS, global analysis of PROtein-Metabolite Interactions using Size separation in Arabidopsis thaliana

ABSTRACT: Herein, we describe a method, dubbed PROMIS that allows simultaneous, global analysis of endogenous protein–small-molecule and protein-protein complexes. To this end a cell-free native lysate was subjected to size-exclusion chromatography followed by quantitative metabolomic and proteomic analysis. Applying this approach to an extract from Arabidopsis thaliana cell cultures, we could retrieve known protein-protein (PPI) and protein–metabolite (PMI) interactions, validating our strategy.

OTHER RELATED OMICS DATASETS IN: MTBLS94

INSTRUMENT(S): Q Exactive

ORGANISM(S): Arabidopsis Thaliana (mouse-ear Cress)

TISSUE(S): Plant Cell, Cell Culture

SUBMITTER: Michal Gorka

LAB HEAD: Aleksandra Skirycz

PROVIDER: PXD009714 | Pride | 2018-06-06

REPOSITORIES: Pride

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	20160705_dv_A04-1108.raw	Raw
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Publications

PROMIS, global analysis of PROtein-metabolite interactions using size separation in Arabidopsis thaliana.

Veyel Daniel D Sokolowska Ewelina M EM Moreno Juan C JC Kierszniowska Sylwia S Cichon Justyna J Wojciechowska Izabela I Luzarowski Marcin M Kosmacz Monika M Szlachetko Jagoda J Gorka Michal M Méret Michaël M Graf Alexander A Meyer Etienne H EH Willmitzer Lothar L Skirycz Aleksandra A

The Journal of biological chemistry 20180531 32

Small molecules not only represent cellular building blocks and metabolic intermediates, but also regulatory ligands and signaling molecules that interact with proteins. Although these interactions affect cellular metabolism, growth, and development, they have been largely understudied. Herein, we describe a method, which we named PROtein-Metabolite Interactions using Size separation (PROMIS), that allows simultaneous, global analysis of endogenous protein-small molec ...[more]

PMID: 29853640

Similar Datasets

Dynamic maps of protein-protein-metabolite complexes of Arabidopsis Thaliana seedlings

Project description:The project aimed to create dynamic maps of protein-protein-metabolite complexes of Arabidopsis thaliana seedlings using PROMIS (PROtein–Metabolite Interactions using Size separation). The approach involves using size exclusion chromatography (SEC) to separate complexes, followed by LC-MS-based proteomics and metabolomics analysis of the obtained fractions. Co-elution is used to reconstruct the protein-metabolite interactions (PMIs) networks. PROMIS strongly progresses understanding protein-small molecule interactions due to its non-targeted manner, cell-wide scale, and generic nature, making it suitable across biological systems. Combining PROMIS with mashing learning approach SLIMP “supervised learning of metabolite-protein interactions from multiple co-fractionation mass spectrometry datasets” allows computing a global map of metabolite-protein interactions in vivo.

2022-10-14 | PXD026713 | Pride

PROMIS, global analysis of PROtein-Metabolite Interactions using Size separation in Arabidopsis thaliana

Project description:Small molecules not only represent cellular building blocks and metabolic intermediates, but also regulatory ligands and signaling molecules that interact with proteins. Although these interactions affect cellular metabolism, growth, and development, they have been largely understudied. Herein, we describe a method, dubbed PROtein-Metabolite Interactions using Size separation (PROMIS) that allows simultaneous, global analysis of endogenous protein-small molecule and of protein‒protein complexes. To this end, a cell-free native lysate from Arabidopsis thaliana cell cultures was fractionated by size-exclusion chromatography, followed by quantitative metabolomic and proteomic analyses. Proteins and small molecules showing similar elution behavior, across protein containing fractions, constituted putative interactors. Applying PROMIS to an A. thaliana extract, we ascertained known protein‒protein (PPIs) and protein-metabolite (PMIs) interactions and reproduced binding between small-molecule protease inhibitors and their respective proteases. More importantly, we present examples of two experimental strategies that exploit the PROMIS dataset to identify novel PMIs. By looking for similar elution behavior of metabolites and enzymes belonging to the same biochemical pathways, we identified putative feedback and feed-forward regulations in pantothenate biosynthesis and the methionine salvage cycle, respectively. By combining PROMIS with an orthogonal affinity purification approach, we identified an interaction between the dipeptide Tyr-Asp and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. In summary, we present proof of concept for a powerful experimental tool that enables system-wide analysis of PMIs and PPIs across all biological systems. The dataset obtained here comprises nearly 140 metabolites and 5000 proteins, which can be mined for putative interactors.

2018-07-19 | MTBLS94 | MetaboLights

Dynamic maps of protein-protein-metabolite complexes in S. cerevisiae

Project description:The project aims to create dynamic maps of protein-protein-metabolite complexes in S. cerevisiae across growth phases using PROMIS (PROtein–Metabolite Interactions using Size separation). It is a biochemical, untargeted, proteome- and metabolome-wide method to study protein-protein and protein–metabolite complexes close to in vivo conditions. Approach involves using size exclusion chromatography (SEC) to separate complexes, followed by LC-MS-based proteomics and metabolomics analysis. This dataset was used for mashie learning approach: SLIMP, supervised learning of metabolite-protein interactions from multiple co-fractionation mass spectrometry datasets, to compute a global map of metabolite-protein interactions.

2022-10-25 | PXD026639 | Pride

PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness

Project description:This study explored the regulatory effect of D-mannose on host immunometabolic responses after viral infection. The results showed that D-mannose can compete with glucose for transporters and hexokinase, inhibiting glycolysis, reducing mitochondrial reactive oxygen species and succinate-induced HIF-1α, thereby reducing virus-induced inflammatory cytokine production. Even with delayed combinatorial treatment of D-mannose and antiviral monotherapy after viral infection, a synergistic effect was still observed in mouse models. Phosphomannose isomerase (PMI) activity determines the benefits of D-mannose, as simultaneous PMI depletion and mannose supplementation impaired cell viability. PMI inhibition can suppress replication of various viruses by affecting host and viral surface protein glycosylation. However, D-mannose does not inhibit PMI activity or viral fitness. In summary, PMI-centered therapeutic strategies can eliminate viral infections, while D-mannose treatment reprograms glycolysis to control collateral damage.

2024-02-13 | GSE255332 | GEO

A global map of protein–metabolite interactions in budding yeast reveals a novel role of a proteogenic dipeptide Ser-Leu in the regulation of a key glycolytic enzyme Pgk1.

Project description:Protein-metabolite interactions (PMIs) are of crucial importance for all cellular processes but remain understudied. Here, we applied a novel biochemical approach named PROMIS, to address the complexity of the protein-small molecule interactome in the model yeast Saccharomyces cerevisiae. By doing so, we provide a unique dataset, which can be queried for novel PMIs between 74 small molecules and 3982 proteins using a user-friendly interface. By interpolating PROMIS with the list of predicted PMIs, we provided experimental validation for 225 binding events. Remarkably, of the 74 small molecules co-eluting with proteins, 36 were proteogenic dipeptides. Targeted analysis of a representative dipeptide, Ser-Leu, revealed numerous protein interactors comprising chaperones, proteasomal subunits, and metabolic enzymes. We could further demonstrate that Ser-Leu binding increases activity of a glycolytic enzyme phosphoglycerate kinase (Pgk1). Consistent with the binding analysis, Ser-Leu supplementation leads to the acute metabolic changes and delays timing of a diauxic shift. Supported by the dipeptide accumulation analysis our work attests to the role of Ser-Leu as a metabolic switch at the interface of protein degradation and central metabolism.

2021-04-26 | PXD021530 | Pride

A miRNome analysis at the early postmortem interval

Project description:The post-mortem interval (PMI) is the time that elapses since the death of an individual until the body is found. Different molecules have been analyzed to better estimate the PMI with variable results. The miRNAs draw attention in the forensic field to estimate the PMI, since they can better support degradation. To find potential biomarkers for PMI estimation, we analyzed the miRNome at early PMI in rat skeletal muscle using the Affymetrix GeneChip™ miRNA 4.0 micoarrays. In this dataset, we include the expression of 1218 rat miRNAs at early postmortem interval.

2023-01-02 | GSE208236 | GEO

Gene-expression profile of breast cancer cell lines and sorted breast cancer epithelial cells

Project description:Most of the breast cancer samples used in clinical research contain multiple cell types other than epithelial cells alone. The non-epithelial cell types have have a substantial effect on the gene expression-profile, which is used to define molecular subtypes of the tumours. The purpose of this data set is to retrieve gene-expression profile within tumour epithelial cells. We collected 9 breast cancer epithelial cell lines and 5 tumour sampes from which epithelial cells were sorted and enriched using BerEp4 antibody coated beads. We profiled the mRNA expression level of these samples and classified probe sets into epithelial genes which were those genes with present calls in at least 50% of the samples. Then we derived an 23-gene signature based on only the epithelial genes to stratify breast cancer. Gene-expression profile analysis of 9 breast cancer epithelial cell lines and 5 tumour epithelium samples purified using BerEp4 antibody coated beads.

2010-08-17 | E-GEOD-23640 | biostudies-arrayexpress

Plasma microRNA signatures for perioperative myocardial injury.

Project description:The pathophysiological mechanism(s) underlying PMI remain controversial. Small non-coding molecules that modulate gene expression may enhance the detection of myocardial injury and provide further mechanistic insight. We profiled plasma exosomal microRNA in patients who sustained PMI after elective non-cardiac surgery

2020-07-26 | GSE144777 | GEO

PROMIS T2D-GENES Exome Sequencing Study

Project description:PROMIS T2D-GENES Exome Sequencing Study

| PRJNA435773 | ENA

PROMIS T2D-GENES Exome Sequencing Study

Project description:PROMIS T2D-GENES Exome Sequencing Study

| PRJNA435774 | ENA