Find research datasets worth reusing

opencc-by-4.0Feb 2020View details →

Supplementary Data to "Disparate regulation of Smad3 phosphorylation and collagen gene transcription by full-length IL-33"

These are Supplementary Figures for the article "Disparate regulation of Smad3 phosphorylation and collagen transcription by full-length IL-33"

MD simulations of phosphorylated peptides (GGXGG)

This repository contains MD simulations and associated analyses of a peptide series of short peptides including phosphorylated residues. It is one of six repositories that are associated to the following research article: <blockquote> Bickel,D., and Vranken,W. (2024) Effects of Phosphorylation on Protein Backbone Dynamics and Conformational Preferences. J. Chem. Theory Comput. https://doi.org/10.1021/acs.jctc.4c00206. </blockquote> The full list of the related repositories is given here: <ol> <li>Pentapeptide simulations: <code>10.5281/zenodo.10517328</code></li> <li>Hexapeptides simulations: <code>10.5281/zenodo.10518872</code></li> <li>Heptapeptides simulations: <code>10.5281/zenodo.10518971</code></li> <li>Octapeptides simulations: <code>10.5281/zenodo.10518993</code></li> <li>Nonapeptides simulations: <code>10.5281/zenodo.10519033</code></li> </ol>

MD simulations of phosphorylated peptides (GGXGXGG)

This repository contains MD simulations and associated analyses of a peptide series of short peptides including phosphorylated residues. It is one of five repositories that are associated to the following research article: <blockquote> Bickel,D., and Vranken,W. (2024) Effects of Phosphorylation on Protein Backbone Dynamics and Conformational Preferences. J. Chem. Theory Comput. https://doi.org/10.1021/acs.jctc.4c00206. </blockquote> The full list of the related repositories is given here: <ol> <li>Pentapeptide simulations: <code>10.5281/zenodo.10517328</code></li> <li>Hexapeptides simulations: <code>10.5281/zenodo.10518872</code></li> <li>Heptapeptides simulations: <code>10.5281/zenodo.10518971</code></li> <li>Octapeptides simulations: <code>10.5281/zenodo.10518993</code></li> <li>Nonapeptides simulations: <code>10.5281/zenodo.10519033</code></li> </ol>

MD simulations of phosphorylated peptides (GGXXGG)

This repository contains MD simulations and associated analyses of a peptide series of short peptides including phosphorylated residues. It is one of five repositories that are associated to the following research article: <blockquote> Bickel,D., and Vranken,W. (2024) Effects of Phosphorylation on Protein Backbone Dynamics and Conformational Preferences. J. Chem. Theory Comput. https://doi.org/10.1021/acs.jctc.4c00206. </blockquote> The full list of the related repositories is given here: <ol> <li>Pentapeptide simulations: <code>10.5281/zenodo.10517328</code></li> <li>Hexapeptides simulations: <code>10.5281/zenodo.10518872</code></li> <li>Heptapeptides simulations: <code>10.5281/zenodo.10518971</code></li> <li>Octapeptides simulations: <code>10.5281/zenodo.10518993</code></li> <li>Nonapeptides simulations: <code>10.5281/zenodo.10519033</code></li> </ol>

MD simulations of phosphorylated peptides (GGXGGXGG)

This repository contains MD simulations and associated analyses of a peptide series of short peptides including phosphorylated residues. It is one of five repositories that are associated to the following research article: <blockquote> Bickel,D., and Vranken,W. (2024) Effects of Phosphorylation on Protein Backbone Dynamics and Conformational Preferences. J. Chem. Theory Comput. https://doi.org/10.1021/acs.jctc.4c00206. </blockquote> The full list of the related repositories is given here: <ol> <li>Pentapeptide simulations: <code>10.5281/zenodo.10517328</code></li> <li>Hexapeptides simulations: <code>10.5281/zenodo.10518872</code></li> <li>Heptapeptides simulations: <code>10.5281/zenodo.10518971</code></li> <li>Octapeptides simulations: <code>10.5281/zenodo.10518993</code></li> <li>Nonapeptides simulations: <code>10.5281/zenodo.10519033</code></li> </ol>

MD simulations of phosphorylated peptides (GGXGGGXGG)

This repository contains MD simulations and associated analyses of a peptide series of short peptides including phosphorylated residues. It is one of five repositories that are associated to the following research article: <blockquote> Bickel,D., and Vranken,W. (2024) Effects of Phosphorylation on Protein Backbone Dynamics and Conformational Preferences. J. Chem. Theory Comput. https://doi.org/10.1021/acs.jctc.4c00206. </blockquote> The full list of the related repositories is given here: <ol> <li>Pentapeptide simulations: <code>10.5281/zenodo.10517328</code></li> <li>Hexapeptides simulations: <code>10.5281/zenodo.10518872</code></li> <li>Heptapeptides simulations: <code>10.5281/zenodo.10518971</code></li> <li>Octapeptides simulations: <code>10.5281/zenodo.10518993</code></li> <li>Nonapeptides simulations: <code>10.5281/zenodo.10519033</code></li> </ol>

opencc-by-4.0Nov 2024View details →

Global comparative structural analysis of responses to protein phosphorylation

This contains the structures and data used for the structural analysis presented in Global comparative structural analysis of responses to protein phosphorylation (Correa Marrero et al., https://doi.org/10.1101/2024.10.18.617420 ). To summarize: <ul> <li>filtered_df.xlsx: dataset of paired phosphorylated structures and their non-phosphorylated counterparts. Each row contains one such pair.</li> <li>chains_by_protein.zip: each directory (named with a UniProt ID) contains the used structures that form the basis for the analysis. The structures are in PDB format, in a separate directory for each protein in the dataset. The exception is the annotation_per_psite directory, which contains annotation as a csv file for each phosphosite.</li> <li>extracted_domains.zip: contains structures of Pfam domains (extracted from the previous dataset) in PDB format. Each filename follows the format {PDB ID}_{Chain ID}_{Pfam domain ID}. The domain_coverage.csv file lists the domain coverage of the structure, as well as its length compared to the whole sequence and the whole structure it was extracted from. These are the structures used for the analysis shown in Fig. 1 f-h.</li> <li>extracted_pfam_domains.zip: contains structures of a broader set Pfam domain structures (the whole set of Pfam domains found to contain a phosphosite in filtered_df.csv) in PDB format. Each directory (named with the Pfam ID) contains the structures. merged_pfam_data.tsv contains metadata about the structures (structure quality, coverage of the domain structure, phosphosite location...). These are the structures used for the analysis shown in Fig. 2.</li> </ul>

opencc-by-4.0Sep 2024View details →

Phosphorylation regulated conformational diversity and topological dynamics of an intrinsically disordered nuclear receptor

Molecular dynamics simulations of AF1c region of human glucocorticoid receptor and its phosphovariants as described in the below paper:  Phosphorylation regulated conformational diversity and topological dynamics of an intrinsically disordered nuclear receptor Vasily Akulov, Alba Jiménez Panizo, Eva Estébanez-Perpiñá, John van Noort, Alireza Mashaghi   The data related to this project has been deposited in two repositories. This repository contains the second part of the data; the first part can be found at DOI: 10.5281/zenodo.13820169

opencc-by-4.0Jul 2024View details →

Molecular Dynamics Trajectories Exploring the Impact of Phosphorylation on the Physiological Form of Human alpha-Synuclein in Aqueous Solution

<h3>Primary data for the publication "Impact of Phosphorylation on the Physiological Form of Human alpha-Synuclein in Aqueous Solution" by de Bruyn, Dorn, Rossetti, Fernandez, Outeiro, Schulz and Carloni. Submitted to the Journal of Chemical Information and Modeling.</h3> Included are all GROMACS input files, parameterised topologies, starting and final configurations, and trajectories for the lowest temperature replica (at 300 K, lowest of 32 replicas between 300-500 K exchanging according to the REST2 algorithm (Wang et al. 2011)). The data is split into three archives: <ol> <li>all_atom_trajectories.zip <ul> <li>contains all input files and all atom trajectories including solvent</li> <li>trajectories written at 100 ps intervals</li> </ul> </li> <li>protein+ion_trajectories.zip <ul> <li>contains configuration/non-parameterised topologies and trajectories excluding solvent, but including ions</li> <li>trajectories written at 10 ps intervals</li> </ul> </li> <li>additional_simulations.zip <ul> <li>contains the all atom trajectories and input files, and</li> <li>solvent-free trajectories above,</li> <li>for the additional simulations in the Supplemental Information of the article: <ul> <li>includes the DES-Amber-based simulations with 64 replicas between 300-600 K, and</li> <li>a99SB-disp-based simulations</li> </ul> </li> </ul> </li> </ol>   Folders are named according to the following top level scheme: <ul> <li>DES-Amber simulations/ Simulations created using the DES-Amber force field (Tucker et al. 2022)</li> <li>a99SB-disp simulations/ SImulations created using the a99SB-disp force field for Intrinsically Disordered Proteins (IDPs) (Robustelli et al. 2018)</li> </ul> Sub-folders follow the following scheme: <ul> <li>AS/ Simulations of the physiological form of wild-type Human α-Synuclein <ul> <li>unphosphorylated</li> </ul> </li> <li>pAS/ Simulations of the physiological form of wild-type Human α-Synuclein <ul> <li>phosphorylated at S129</li> <li>with double negative charge</li> </ul> </li> <li>pASH/ Simulations of the physiological form of wild-type Human α-Synuclein (a99SB-disp simulations only) <ul> <li>phosphorylated at S129</li> <li>with a single negative charge (monoprotonated)</li> </ul> </li> </ul>

opencc-by-4.0Oct 2022View details →

Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis

Abstract Vascular endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in diseases such as cancer and retinopathies. Inhibitors of Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin tyrosine phosphorylation and prevent excessive leakage, edema and high interstitial pressure. Here we show that the Src-related Yes tyrosine kinase, rather than Src, is localized at endothelial cell (EC) junctions where it becomes activated in a flow-dependent manner. EC-specific Yes1 deletion suppresses VE-cadherin phosphorylation and arrests VE-cadherin at EC junctions. This is accompanied by loss of EC collective migration and exaggerated agonist-induced macromolecular leakage. Overexpression of Yes1 causes ectopic VE-cadherin phosphorylation, while vascular leakage is unaffected. In contrast, in EC-specific Src-deficiency, VE-cadherin internalization is maintained, and leakage is suppressed. In conclusion, Yes-mediated phosphorylation regulates constitutive VE-cadherin turnover, thereby maintaining endothelial junction plasticity and vascular integrity. Method for retinal EC distribution analysis Chimeric recombination was induced in iSuRe-Cre+ mice at P3 by i.p. injection of tamoxifen (100 µg/mouse, Sigma). Retinas were taken at P7 and P15, immunostained for CD31 and flat-mounted. Images were taken by z-stack tile scanning using a 10X objective on a confocal microscope (Leica SP8). Maximum intensity projection images of whole retinas were used for image segmentation, which was performed with ImageJ resources. The maximum projection of the MbTomato channel threshold was established to distinguish MbTomato+ cells from the background. Outliers with a radius between 0.2-1.0 µm were removed. The CD31 channel (after maximum projection) was used to define the outlines of veins and arteries; the optic nerve was used as a mask to define a referential system. For computational analysis, a bespoken Python-based workflow was employed, accessible on GitHub (https://github.com/wgiese/retina-vein-artery-cs). For every pixel in the image, three numbers were computed (using the mask as referential): (1) distance to the nearest vein (dv), (2) distance to the nearest artery (da) and (3) radial distance to the optic nerve (r). From these measures, the relative distances by ϕv-a = dv/(dv + da) were obtained. The EC distribution was computed by performing the operation for all YFP-positive pixels, which were used as a proxy for EC distribution. A kernel density estimation was used to approximate the underlying EC distribution in the 2D coordinate system spanned by ϕv-a and r.

opencc-by-4.0Jun 2023View details →

Source data for "Regulation of replication origin licensing by ORC phosphorylation reveals a two-step mechanism for Mcm2-7 ring closing"

Source data for "Regulation of replication origin licensing by ORC phosphorylation reveals a two-step mechanism for Mcm2-7 ring closing"  The data is organized by Figure and associated Supp Figure(s). A README file is included in each figure folder to explain the files. (note: Data is included for Figs2-7 and SuppFigs 2-8. Fig.1 and SuppFig.1 did not have any associated data matrices, so there is no upload for them here).  Briefly, the single molecule data is included in several different formats, all generated from single-molecule TIRF-microscopy video files using Matlab: Integrated trace files "traces" include integrated fluorescence intensity at individual DNA molecules over a 20 minute reaction. Background-corrected trace files normalize the integrated fluorescence intensity to a local-average background, as described in the Methods section of the paper-- these are used for EFRET calculations. "Intervals" files include the start, end time, and duration of protein-DNA interactions and were generated from the trace files and the raw videos using the Imscroll program (available at: https://github.com/gelles-brandeis/CoSMoS_Analysis). EFRET vectors are concatenated vectors of the EFRET vs time values of all protein-DNA interactions in the experiment-- these are used to generate EFRET heat maps.  Matlab analysis scripts used in the paper are uploaded in a separate folder "ALA_scripts_used_final". Several of these scripts reference custom Matlab functions from the Gelles lab which are available here: https://github.com/gelles-brandeis/jganalyze and should be downloaded along with my attached scripts file.  note: Raw single-molecule video files have not been uploaded here due to large sizes, but can be provided upon request.

opencc-by-4.0Dec 2020View details →

Simulation Data for "How GPCR phosphorylation patterns orchestrate arrestin-mediated signaling"

Simulation data and analysis code for Latorraca, Masureel et al., How GPCR Phosphorylation Patterns Orchestrate Arrestin-Mediated Signaling, Cell (2020), https://doi.org/10.1016/j.cell.2020.11.014. Please see included readme files for more information.

opencc-zeroSep 2019View details →

Data from: Sperm competitive advantage of a rare mitochondrial haplogroup linked to differential expression of mitochondrial oxidative phosphorylation genes

Maternal inheritance of mitochondria creates a sex-specific selective sieve through which mitochondrial mutations harmful to males but not females accumulate and contribute to sexual differences in longevity and disease susceptibility. Because eggs and sperm are under disruptive selection, sperm are predicted to be particularly vulnerable to the genetic load generated by maternal inheritance, yet evidence for mitochondrial involvement in male fertility is limited and controversial. Here, we exploit the coexistence of two divergent mitochondrial haplogroups (A and B2) in a Neotropical arachnid to investigate the role of mitochondria in sperm competition. DNA profiling demonstrated that B2-carrying males sired more than three times as many offspring in sperm competition experiments than A males, and this B2 competitive advantage cannot be explained by female mitochondrial haplogroup or male nuclear genetic background. RNA-Seq of testicular tissues implicates differential expression of mitochondrial oxidative phosphorylation (OXPHOS) genes in the B2 competitive advantage, including a 22-fold upregulation of atp8 in B2 males. Previous comparative genomic analyses have revealed functionally significant amino acid substitutions in differentially expressed genes, indicating that the mitochondrial haplogroups differ not only in expression but also in DNA sequence and protein functioning. However, mitochondrial haplogroup had no effect on sperm number or sperm viability, and, when females were mated to a single male, neither male haplogroup, female haplogroup nor the interaction between male/female haplogroup significantly affected female reproductive success. Our findings therefore suggest that mitochondrial effects on male reproduction may often go undetected in noncompetitive contexts and may prove more important in nature than is currently appreciated.

opencc-by-4.0Dec 2022View details →

Serine-129 phosphorylation of a-synuclein is an activity-dependent trigger for physiologic protein-protein interactions and synaptic function

Phosphorylation of a-synuclein at the Serine-129 site (a-syn Ser129P) is an established pathologic hallmark of synucleinopathies and a therapeutic target. In physiologic states, only a small fraction of a-syn is phosphorylated at this site, and most studies have focused on the pathologic roles of this post-translational modification. We found that unlike wild-type (WT) a-syn which is widely expressed throughout the brain, the overall pattern of a-syn Ser129P is restricted, suggesting intrinsic regulation. Surprisingly, preventing Ser129P blocked activity-dependent synaptic attenuation by a-syn – thought to reflect its normal function. Exploring mechanisms, we found that neuronal activity augments Ser129P, which is a trigger for protein-protein interactions that are necessary for mediating a-syn function at the synapse. AlphaFold2-driven modeling and membrane-binding simulations suggest a scenario where Ser129P induces conformational changes that facilitate interactions with binding partners. Our experiments offer a new conceptual platform for investigating the role of Ser129 in synucleinopathies, with implications for drug-development.

opencc-by-4.0Dec 2023View details →

Quantification of phosphorylated metabolites, organic acids, and intermediates of the TCA cycle using capillary ion chromatography tandem mass spectrometry (capIC-MS/MS) following treatment of Escherichia coli with ciprofloxacin

Capillary ion chromatography tandem mass spectrometry (capIC-MS/MS) was used to quantify phosphorylated metabolites, organic acids, and intermediates of the TCA cycle of Escherichia coli treated with ciprofloxacin, BTP-001 (a novel antimicrobial peptide), and a combination of the two . Metabolite extracts were analyzed with a Xevo TQ-XS triple quadrupole mass spectrometer (Waters, USA).Samples were gathered from E. coli cultures grown in batch cultivations using 1 liter bioreactors. Briefly, intracellular metabolites were extracted by cycling samples between −20 °C EtOH and N2 (l) in three consecutive freeze–thaw cycles, with vortexing every 10 min during the thawing phase. Filters were removed and the cell debris was pelleted (4500 rcf, 10 min, -9 °C). The supernatants were transferred to a new tube, snap frozen in N2 (l), and lyophilized. Lyophilized extracts were reconstituted in 500 µL cold Milli-Q H2O and cleared by spin-filtration with a 10 kDa molecular cutoff (20817 rcf, 10 min, 0 °C). A mix of 80 µL centrifuged sample and 20 µL 13C-labeled ISTD extract from yeast was sent to analysis. Data processing and absolute quantification was performed as earlier described using the TargetLynx application manager of MassLynx v 4.1 (Waters) to interpolate calibration curves made with appropriate dilutions of analytical grade standards (Sigma-Aldrich). The response factor of the corresponding U13C-isotopologues were used to correct the standard and sample extract response factors. Extract concentrations were normalized to the CDW, which was calculated from interpolation of the OD600 vs. CDW (g/L) curve. Further statistical analysis in MetaboAnalyst v 5.0 replaced missing values with 1/5 of the minimum value of the respective metabolite. An unpaired T-test with unequal variance determined differential enriched metabolites with a false discovery rate (FDR) < 0.05 which are presented as log2 fold-change compared to control.

opencc-zeroJan 2024View details →

Saccharomyces cerevisiae protein phosphorylation and translation accuracy

Protein-protein and protein-rRNA interactions involving ribosomal proteins uS4 and uS5 are thought to maintain the accuracy of protein synthesis by increasing selection of cognate aminoacyl-tRNAs. Selectivity involves a major conformational change—domain closure—that stabilizes aminoacyl-tRNA in the ribosomal acceptor (A) site. This has been thought a constitutive function of the ribosome ensuring consistent accuracy. Recently, the Saccharomyces cerevisiae Ctk1 cyclin-dependent kinase was demonstrated to ensure translational accuracy and Ser238 of uS5 proposed as its target. Surprisingly, Ser238 is outside the uS4-uS5 interface and no obvious mechanism has been proposed to explain its role. We show that the true target of Ctk1 regulation is another uS5 residue, Ser176, which lies in the interface opposite to Arg57 of uS4. Based on site-specific mutagenesis, we propose that phospho-Ser176 forms a salt bridge with Arg57, which should increase selectivity by strengthening the interface. Genetic data show that Ctk1 regulates accuracy indirectly by stimulating phosphorylation of Ser176 by the kinase Ypk2. A second kinase pathway involving TORC1 and Pkc1 can inhibit this effect. The level of accuracy appears to depend on competitive action of these two pathways to regulate the level of Ser176 phosphorylation.

opencc-zeroFeb 2024View details →

Data from: Phosphorylation, disorder, and phase separation govern the behavior of Frequency in the fungal circadian clock

Circadian clocks are composed of molecular oscillators that pace rhythms of gene expression to the diurnal cycle. Therein, transcriptional-translational negative feedback loops (TTFLs) generate oscillating levels of transcriptional repressor proteins that regulate their own gene expression. In the filamentous fungus Neurospora crassa, the proteins Frequency (FRQ), the FRQ-interacting RNA helicase (FRH) and Casein-Kinase I (CK1) form the FFC complex that represses expression of genes activated by the White-Collar complex (WCC). A key question concerns how FRQ orchestrates molecular interactions at the core of the clock despite containing little predicted tertiary structure. We present the reconstitution and biophysical characterization of FRQ and the FFC in unphosphorylated and highly phosphorylated states. Site-specific spin labeling and pulse-dipolar ESR spectroscopy provides domain-specific structural details on the full-length, 989-residue intrinsically disordered FRQ and the FFC. FRQ contains a compact core that associates and organizes FRH and CK1 to coordinate their roles in WCC repression. FRQ phosphorylation increases conformational flexibility and alters oligomeric state but the changes in structure and dynamics are non-uniform. Full-length FRQ undergoes liquid-liquid phase separation (LLPS) to sequester FRH and CK1 and influence CK1 enzymatic activity. Although FRQ phosphorylation favors LLPS, LLPS feeds back to reduce FRQ phosphorylation by CK1 at higher temperatures. Live imaging of Neurospora hyphae reveals FRQ foci characteristic of condensates near the nuclear periphery. Analogous clock repressor proteins in higher organisms share little position-specific sequence identity with FRQ; yet, they contain amino-acid compositions that promote LLPS. Hence, condensate formation may be a conserved feature of eukaryotic circadian clocks.

opencc-zeroApr 2024View details →

Data for: A novel and ubiquitous miRNA-involved regulatory module ensures precise phosphorylation of RNA polymerase II and proper transcription

Proper transcription orchestrated by RNA polymerase II (RNPII) is crucial for cellular development, which relies on the phosphorylation state of RNPII's carboxyl-terminal domain (CTD). Sporangia, developed from mycelia, are essential for the destructive oomycetes Phytophthora, remarkable transcriptional changes are observed during the morphological transition. However, how these changes are rapidly triggered and their relationship with the versatile RNPII-CTD phosphorylation remain enigmatic. Herein, we found that Phytophthora capsici had undergone an elevation of Ser5-phosphorylation in its uncanonical heptapeptide repeats of RNPII-CTD during sporangia development, which subsequently changed the chromosomal occupation of RNPII and primarily activated transcription of certain genes. A cyclin-dependent kinase, PcCDK7, was highly induced and phosphorylated RNPII-CTD during this morphological transition. Mechanistically, a novel DCL1-dependent microRNA, pcamiR1, was found to be a feedback modulator for the precise phosphorylation of RNPII-CTD by complexing with PcAGO1 and regulating the accumulation of PcCDK7. Moreover, this study revealed that the pcamiR1-CDK7-RNPII regulatory module is evolutionarily conserved and the impairment of the balance between pcamiR1 and PcCDK7 could efficiently reduce the growth and virulence of P. capsici. Collectively, this study uncovers a novel and evolutionarily conserved mechanism of transcription regulation that could facilitate correct development and identifies pcamiR1 as a promising target for disease control.

opencc-by-4.0May 2022View details →

Original data for publication: The Atomically Precise Gold/Captopril Nanocluster Au25(Capt)18 Gains Anticancer Activity by Inhibiting Mitochondrial Oxidative Phosphorylation

Original data for publication: The Atomically Precise Gold/Captopril Nanocluster Au25(Capt)18 Gains Anticancer Activity by Inhibiting Mitochondrial Oxidative Phosphorylation, ACS Applied Materials & Interfaces