Global Landscape of Native Protein Complexes in<i>Synechocystis</i>sp. PCC 6803

Xu, Chen; Wang, Bing; Yang, Lin; Hu, Lucas; Yi, Lanxing; Wang, Yaxuan; Chen, Shenglan; Emili, Andrew; Wan, Cuihong

doi:10.1101/2020.03.07.980128

Cited by 5 publications

(4 citation statements)

References 75 publications

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“…While there are reports on the composition of protein complexes (Xu et al, 2020) and the association of these complexes with the thylakoid or cell membrane systems in the model Synechocystis (Baers et al, 2019), no information on RNA/protein complexes is currently available for any cyanobacterium. Here, we report the results of Grad-seq analysis applied to Synechocystis, identifying the sedimentation profiles of thousands of transcripts and proteins simultaneously.…”

Section: Introductionmentioning

confidence: 99%

Analysis of a photosynthetic cyanobacterium rich in internal membrane systems via gradient profiling by sequencing (Grad-seq)

Riediger

Spät

Bilger

et al. 2020

Preprint

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AbstractRegulatory sRNAs in photosynthetic cyanobacteria have been reported, but the lack of plausible RNA chaperones involved in this regulation appears enigmatic. Here, we analyzed the full ensemble of cellular RNAs and cofractionating proteins using gradient profiling by sequencing (Grad-seq) in Synechocystis 6803. Complexes with overlapping subunits such as the CpcG1-type versus the CpcL-type phycobilisomes or the PsaK1 versus PsaK2 photosystem I pre(complexes) could be distinguished supporting a high quality of the approach. Clustering of the in-gradient distribution profiles followed by several additional criteria yielded a short list of potential RNA chaperones that include a YlxR homolog and a cyanobacterial homolog of the KhpA/B complex. The data suggest previously undetected complexes between accessory proteins and CRISPR-Cas systems, such as a Csx1-Csm6 ribonucleolytic defense complex. Moreover, the exclusive association of either RpoZ or 6S RNA with the core RNA polymerase complex and the existence of a reservoir of inactive sigma-antisigma complexes is suggested. The Synechocystis Grad-seq resource is available online at https://trex90.shinyapps.io/GradSeqExplorer_SynPCC6803/, providing a comprehensive resource for the functional assignment of RNA-protein complexes and multisubunit protein complexes in a photosynthetic organism.

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Section: Introductionmentioning

confidence: 99%

Analysis of a photosynthetic cyanobacterium rich in internal membrane systems via gradient profiling by sequencing (Grad-seq)

Riediger

Spät

Bilger

et al. 2020

Preprint

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“…Network modularity analysis-such as used to identify protein complexes in protein-protein interaction network [42][43][44][45][46][47] , for instance-represents an effective mean to identify subset of drugs (modules) presenting high intra-module and low-extramodule MoA conservation. In addition, this can be used to identify individual drugs with strong MoA conservation spanning across two or more modules, thus indicating potential polypharmacology.…”

Section: Moa Similarity Network Modularity Analysismentioning

confidence: 99%

Elucidating Compound Mechanism of Action and Polypharmacology with a Large-scale Perturbational Profile Compendium

Hu,

Douglass,

Turunen

et al. 2023

Preprint

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The Mechanism of Action (MoA) of a drug is generally represented as a small, non-tissue-specific repertoire of high-affinity binding targets. Yet, drug activity and polypharmacology are increasingly associated with a broad range of off-target and tissue-specific effector proteins. To address this challenge, we have implemented an efficient integrative experimental and computational framework leveraging the systematic generation and analysis of drug perturbational profiles representing >700 FDA-approved and experimental oncology drugs, in cell lines selected as high-fidelity models of 23 aggressive tumor subtypes. Protein activity-based analyses revealed highly reproducible, drug-mediated modulation of tissue-specific targets, leading to generation of a proteome-wide polypharmacology map, characterization of MoA-related drug clusters and off-target effects, and identification and experimental validation of novel, tissue-specific inhibitors of undruggable oncoproteins. The proposed framework, which is easily extended to elucidating the MoA of novel small-molecule libraries, could help support more systematic and quantitative approaches to precision oncology.

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“…PCC 6803 2062 proteins, 291 multiprotein complexes Yes Global landscape of native protein complexes in Synechocystis sp . Pcc 6803 [25] SEC S. cerevisiae (log-phase) 3982 proteins, 74 metabolites Yes Global mapping of protein–metabolite interactions in Saccharomyces cerevisiae reveals that Ser-Leu dipeptide regulates phosphoglycerate kinase activity [17] SEC Chaetomium thermophilum 3286 proteins, 257 metabolites No Coupling proteomics and metabolomics for the unsupervised identification of protein-metabolite interactions in Chaetomium thermophilum [15] …”

Section: Background and Summarymentioning

confidence: 99%

PROMISed: A novel web-based tool to facilitate analysis and visualization of the molecular interaction networks from co-fractionation mass spectrometry (CF-MS) experiments

Schlossarek

Luzarowski

Sokołowska

et al. 2021

Computational and Structural Biotechnology Journal

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Co-fractionation mass spectrometry (CF-MS)-based approaches enable cell-wide identification of protein-protein and protein-metabolite complexes present in the cellular lysate. CF-MS combines biochemical separation of molecular complexes with an untargeted mass-spectrometry-based proteomics and/or metabolomics analysis of the obtained fractions, and is used to delineate putative interactors. CF-MS data are a treasure trove for biological discovery. To facilitate analysis and visualization of original or publically available CF-MS datasets, we designed PROMISed, a user-friendly tool available online via https://myshiny.mpimp-golm.mpg.de/PDP1/ or as a repository via https://github.com/DennisSchlossarek/PROMISed . Specifically, starting with raw fractionation profiles, PROMISed (i) contains activities for data pre-processing and normalization, (ii) deconvolutes complex fractionation profiles into single, distinct peaks, (iii) identifies co-eluting protein–protein or protein–metabolite pairs using user-defined correlation methods, and (iv) performs co-fractionation network analysis. Given multiple CF-MS datasets, for instance representing different environmental condition, PROMISed allows to select for proteins and metabolites that differ in their elution profile, which may indicate change in the interaction status. But it also enables the identification of protein–protein and protein–metabolite pairs that co-elute together across multiple datasets. PROMISed enables users to (i) easily adjust parameters at each step of the analysis, (ii) download partial and final results, and (iii) select among different data-visualization options. PROMISed renders CF-MS data accessible to a broad scientific audience, allowing users with no computational or statistical background to look for novel protein–protein and protein–metabolite complexes for further experimental validation.

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Global Landscape of Native Protein Complexes inSynechocystissp. PCC 6803

Cited by 5 publications

References 75 publications

Analysis of a photosynthetic cyanobacterium rich in internal membrane systems via gradient profiling by sequencing (Grad-seq)

Analysis of a photosynthetic cyanobacterium rich in internal membrane systems via gradient profiling by sequencing (Grad-seq)

Elucidating Compound Mechanism of Action and Polypharmacology with a Large-scale Perturbational Profile Compendium

PROMISed: A novel web-based tool to facilitate analysis and visualization of the molecular interaction networks from co-fractionation mass spectrometry (CF-MS) experiments

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