scholarly journals Cloud Prediction of Protein Structure and Function with PredictProtein for Debian

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
László Kaján ◽  
Guy Yachdav ◽  
Esmeralda Vicedo ◽  
Martin Steinegger ◽  
Milot Mirdita ◽  
...  
Keyword(s):  
High Performance ◽  
Solvent Accessibility ◽  
Protein Coding ◽  
Nuclear Localization Signals ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Coding Regions ◽  
Standard Set ◽  
And Function ◽  
Performance Computing

We report the release of PredictProtein for the Debian operating system and derivatives, such as Ubuntu, Bio-Linux, and Cloud BioLinux. The PredictProtein suite is available as a standard set of open source Debian packages. The release covers the most popular prediction methods from the Rost Lab, including methods for the prediction of secondary structure and solvent accessibility (profphd), nuclear localization signals (predictnls), and intrinsically disordered regions (norsnet). We also present two case studies that successfully utilize PredictProtein packages for high performance computing in the cloud: the first analyzes protein disorder for whole organisms, and the second analyzes the effect of all possible single sequence variants in protein coding regions of the human genome.

scholarly journals Intrinsically disordered proteins identified in the aggregate proteome serve as biomarkers of neurodegeneration

2021 ◽  
Author(s):  
Srinivas Ayyadevara ◽  
Akshatha Ganne ◽  
Meenakshisundaram Balasubramaniam ◽  
Robert J. Shmookler Reis
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Protein Complexes ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Physiological Processes ◽  
Protein Partners ◽  
And Function ◽  
Computational Analyses ◽  
Disordered Regions

AbstractA protein’s structure is determined by its amino acid sequence and post-translational modifications, and provides the basis for its physiological functions. Across all organisms, roughly a third of the proteome comprises proteins that contain highly unstructured or intrinsically disordered regions. Proteins comprising or containing extensive unstructured regions are referred to as intrinsically disordered proteins (IDPs). IDPs are believed to participate in complex physiological processes through refolding of IDP regions, dependent on their binding to a diverse array of potential protein partners. They thus play critical roles in the assembly and function of protein complexes. Recent advances in experimental and computational analyses predicted multiple interacting partners for the disordered regions of proteins, implying critical roles in signal transduction and regulation of biological processes. Numerous disordered proteins are sequestered into aggregates in neurodegenerative diseases such as Alzheimer’s disease (AD) where they are enriched even in serum, making them good candidates for serum biomarkers to enable early detection of AD.

scholarly journals Combinatorial phosphorylation modulates the structure and function of the G protein γ subunit in yeast

2021 ◽  
Vol 14 (688) ◽  
pp. eabd2464
Author(s):  
Zahra Nassiri Toosi ◽  
Xinya Su ◽  
Ruth Austin ◽  
Shilpa Choudhury ◽  
Wei Li ◽  
...  
Keyword(s):  
G Protein ◽  
Posttranslational Modifications ◽  
Intrinsically Disordered Proteins ◽  
Structure And Function ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Gpcr Activation ◽  
Essential Components ◽  
And Function

Intrinsically disordered regions (IDRs) in proteins are often targets of combinatorial posttranslational modifications, which serve to regulate protein structure and function. Emerging evidence suggests that the N-terminal tails of G protein γ subunits, which are essential components of heterotrimeric G proteins, are intrinsically disordered, phosphorylation-dependent determinants of G protein signaling. Here, we found that the yeast Gγ subunit Ste18 underwent combinatorial, multisite phosphorylation events within its N-terminal IDR. G protein–coupled receptor (GPCR) activation and osmotic stress induced phosphorylation at Ser7, whereas glucose and acid stress induced phosphorylation at Ser3, which was a quantitative indicator of intracellular pH. Each site was phosphorylated by a distinct set of kinases, and phosphorylation of one site affected phosphorylation of the other, as determined through exposure to serial stimuli and through phosphosite mutagenesis. Last, we showed that phosphorylation resulted in changes in IDR structure and that different combinations of phosphorylation events modulated the activation rate and amplitude of the downstream mitogen-activated protein kinase Fus3. These data place Gγ subunits among intrinsically disordered proteins that undergo combinatorial posttranslational modifications that govern signaling pathway output.

scholarly journals The ArathEULS3 Lectin Ends up in Stress Granules and Can Follow an Unconventional Route for Secretion

2020 ◽  
Vol 21 (5) ◽  
pp. 1659
Author(s):  
Malgorzata Dubiel ◽  
Tibo De De Coninck ◽  
Vinicius Jose Silva Osterne ◽  
Isabel Verbeke ◽  
Daniël Van Van Damme ◽  
...  
Keyword(s):  
Stress Granules ◽  
Protein Translation ◽  
Bioinformatics Analyses ◽  
Lectin Domain ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Terminal Domain ◽  
Unknown Structure ◽  
Stressed Cells ◽  
And Function

Stress granules are cytoplasmic compartments, which serve as mRNA storage units during stress, therefore regulating translation. The Arabidopsis thaliana lectin ArathEULS3 has been widely described as a stress inducible gene. This study aimed to examine in detail the localization of ArathEULS3 lectin in normal and stressed cells. Colocalization experiments revealed that the nucleo-cytoplasmic lectin ArathEULS3 relocates to stress granules after stress. The ArathEULS3 sequence encodes a protein with a EUL lectin domain and an N-terminal domain with unknown structure and function. Bioinformatics analyses showed that the N-terminal domain sequence contains intrinsically disordered regions and likely does not exhibit a stable protein fold. Plasmolysis experiments indicated that ArathEULS3 also localizes to the apoplast, suggesting that this protein might follow an unconventional route for secretion. As part of our efforts we also investigated the interactome of ArathEULS3 and identified several putative interaction partners important for the protein translation process.

scholarly journals Beyond Microsatellite Instability: Intrinsic Disorder as a Potential Link Between Protein Short Tandem Repeats and Cancer

2021 ◽  
Vol 1 ◽  
Author(s):  
Max A. Verbiest ◽  
Matteo Delucchi ◽  
Tugce Bilgin Sonay ◽  
Maria Anisimova
Keyword(s):  
Amino Acids ◽  
Microsatellite Instability ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Disordered Proteins ◽  
Future Research ◽  
Protein Coding ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Short Tandem

Short tandem repeats (STRs) are abundant in genomic sequences and are known for comparatively high mutation rates; STRs therefore are thought to be a potent source of genetic diversity. In protein-coding sequences STRs primarily encode disorder-promoting amino acids and are often located in intrinsically disordered regions (IDRs). STRs are frequently studied in the scope of microsatellite instability (MSI) in cancer, with little focus on the connection between protein STRs and IDRs. We believe, however, that this relationship should be explicitly included when ascertaining STR functionality in cancer. Here we explore this notion using all canonical human proteins from SwissProt, wherein we detected 3,699 STRs. Over 80% of these consisted completely of disorder promoting amino acids. 62.1% of amino acids in STR sequences were predicted to also be in an IDR, compared to 14.2% for non-repeat sequences. Over-representation analysis showed STR-containing proteins to be primarily located in the nucleus where they perform protein- and nucleotide-binding functions and regulate gene expression. They were also enriched in cancer-related signaling pathways. Furthermore, we found enrichments of STR-containing proteins among those correlated with patient survival for cancers derived from eight different anatomical sites. Intriguingly, several of these cancer types are not known to have a MSI-high (MSI-H) phenotype, suggesting that protein STRs play a role in cancer pathology in non MSI-H settings. Their intrinsic link with IDRs could therefore be an attractive topic of future research to further explore the role of STRs and IDRs in cancer. We speculate that our observations may be linked to the known dosage-sensitivity of disordered proteins, which could hint at a concentration-dependent gain-of-function mechanism in cancer for proteins containing STRs and IDRs.

scholarly journals Applications of Metagenomics for Unrevealing the Extended Horizons of Microbiota Prevalence from Soil to Human Health

2021 ◽  
Vol 15 (1) ◽  
pp. 177-187
Author(s):  
Vrishty Sharma ◽  
Muneer Ahmad Malla ◽  
Rajesh Kumar Kori ◽  
Rajesh Singh Yadav ◽  
Zaffar Azam
Keyword(s):  
Dna Sequencing ◽  
High Performance ◽  
Genetic Material ◽  
Microbial Life ◽  
Adverse Conditions ◽  
Culture Independent ◽  
Depth Study ◽  
Extensive Information ◽  
And Function ◽  
Performance Computing

Phylogenetic analysis of different ecosystems has shown that the number of microbial communities in a single sample exceeds their cultured counterparts. Microbes have been found throughout nature and can thrive in adverse conditions. Besides inhabiting diverse environments, they also play a key role in the maintenance of the ecosystem. Most of these microbes are either unculturable or difficult to culture with conventional culturing methods. Metagenomics is an emerging field of science that has been in the light for a decade and offers a potential way to assess microbial diversity. The development of metagenomics opens new ways to study genetic material directly from the environmental samples. DNA sequencing and synthesis technologies are making it possible to read and write entire genomes. The huge amount of data obtained from genome sequencing inevitably requires bioinformatics tools to handle and further process them for analysis. Advances in DNA sequencing and high-performance computing have brought about exemplar improvement in metagenomics, allowing in-depth study of the largely unexplored frontier of microbial life. This culture-independent method provides extensive information regarding the structure, composition, and function of the diverse assemblages of the environmental microbes. The current review presents an overview of the technical aspects of metagenomics along with its diverse applications.

scholarly journals Combinatorial phosphorylation modulates the structure and function of the G protein gamma subunit in yeast

2020 ◽  
Author(s):  
Zahra Nassiri Toosi ◽  
Xinya Su ◽  
Shilpa Choudhury ◽  
Wei Li ◽  
Yui Tik Pang ◽  
...  
Keyword(s):  
G Protein ◽  
Intrinsically Disordered Proteins ◽  
Protein Complexes ◽  
Disordered Proteins ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Gpcr Activation ◽  
Essential Components ◽  
And Function

AbstractProtein intrinsically disordered regions (IDRs) are often targets of combinatorial post-translational modifications (PTMs) that serve to regulate protein structure and/or function. Emerging evidence suggests that the N-terminal tails of G protein γ subunits – essential components of heterotrimeric G protein complexes – are intrinsically disordered, highly phosphorylated governors of G protein signaling. Here, we demonstrate that the yeast Gγ Ste18 undergoes combinatorial, multi-site phosphorylation within its N-terminal IDR. Phosphorylation at S7 is responsive to GPCR activation and osmotic stress while phosphorylation at S3 is responsive to glucose stress and is a quantitative indicator of intracellular pH. Each site is phosphorylated by a distinct set of kinases and both are also interactive, such that phosphomimicry at one site affects phosphorylation on the other. Lastly, we show that phosphorylation produces subtle yet clear changes in IDR structure and that different combinations of phosphorylation modulate the activation rate and amplitude of the scaffolded MAPK Fus3. These data place Gγ subunits among the growing list of intrinsically disordered proteins that exploit combinatorial post-translational modification to govern signaling pathway output.

scholarly journals Identification and quantification of modified nucleosides inSaccharomyces cerevisiaemRNAs

2018 ◽  
Author(s):  
Mehmet Tardu ◽  
Qishan Lin ◽  
Kristin S. Koutmou
Keyword(s):  
Mass Spectrometry ◽  
High Throughput ◽  
Rna Structure ◽  
High Performance ◽  
Modified Nucleosides ◽  
Yeast Cells ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Liquid Chromatography Tandem Mass ◽  
And Function

ABSTRACTPost-transcriptional nucleoside modifications have long been recognized as key modulators of non-coding RNA structure and function. There is an emerging appreciation that the chemical modification of protein-coding messenger RNAs (mRNAs) also plays critical roles in the cell. Although there are over 100 known RNA modifications found in biology only a handful have been identified in mRNAs. We sought to identify and quantify modifications present in the mRNAs of yeast cells using a high throughput ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method that measures the levels of 36 types of RNA nucleosides in parallel. We detected the presence of six modified nucleosides in mRNAs at relatively high abundances: N7-methylguanosine, N6-methyladenosine, 2’-O-methylguanosine, 2’-O-methylcytosine, N4-acetylcytidine and 5-formylcytidine. Additionally, we investigated how the levels of mRNA modifications vary in response to cellular stress. We find that the concentrations of mRNA modifications including N6-methyladenosine and N4-acetylcytidine change in response to heat stress, glucose starvation and/or oxidative stress. This work expands the repertoire of potential chemical modifications in mRNAs, and utilizes a high-throughput approach to search for modifications that highlights the value of integrating mass-spectrometry tools in the mRNA modification discovery and characterization pipeline.

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