scholarly journals The evolution of gene duplicates in angiosperms and the impact of protein-protein interactions and the mechanism of duplication

2019 ◽  
Author(s):  
Jonas Defoort ◽  
Yves Van de Peer ◽  
Lorenzo Carretero-Paulet
Keyword(s):  
Protein Interactions ◽  
Specific Property ◽  
Small Scale ◽  
Biological Interactions ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Functional Dynamics ◽  
Dosage Balance ◽  
Gene Duplicates ◽  
The Impact

Abstract Gene duplicates, generated either through whole genome duplication (WGD) or small-scale duplication (SSD), are prominent in angiosperms and are believed to play an important role in adaptation and in generating evolutionary novelty. Previous studies reported contrasting evolutionary and functional dynamics of duplicate genes depending on the mechanism of origin, a behaviour that is hypothesized to stem from constraints to maintain the relative dosage balance between the genes concerned and their interaction context. However, the mechanisms ultimately influencing loss and retention of gene duplicates over evolutionary time are not yet fully elucidated. Here, by using a robust classification of gene duplicates in Arabidopsis thaliana, Solanum lycopersicum and Zea mays, large RNAseq expression compendia and an extensive protein-protein interaction (PPI) network from Arabidopsis, we investigated the impact of PPIs on the differential evolutionary and functional fate of WGD and SSD duplicates. In all three species, retained WGD duplicates show stronger constraints to diverge at the sequence and expression level than SSD ones, a pattern that is also observed for shared PPI partners between Arabidopsis duplicates. PPIs are preferentially distributed among WGD duplicates and specific functional categories. Furthermore, duplicates with PPIs tend to be under stronger constraints to evolve than their counterparts without PPIs regardless of their mechanism of origin. Our results support dosage balance constraint as a specific property of genes involved in biological interactions, including physical PPIs, and suggest that additional factors may be differently influencing the evolution of genes following duplication, depending on the species, time and mechanism of origin.

scholarly journals Proteomic Analysis of Antigen 60 Complex of M. bovis Bacillus Calmette-Guérin Reveals Presence of Extracellular Vesicle Proteins and Predicted Functional Interactions

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 80 ◽  
Author(s):  
Khayriyyah Mohd Hanafiah ◽  
Norsyahida Arifin ◽  
Paul R. Sanders ◽  
Nurulhasanah Othman ◽  
Mary L. Garcia ◽  
...  
Keyword(s):  
Western Blot ◽  
Protein Interactions ◽  
Ribosomal Proteins ◽  
Vaccine Development ◽  
Extracellular Vesicle ◽  
Biological Interactions ◽  
Bacillus Calmette Guerin ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Antigen 60

Tuberculosis (TB) is ranked among the top 10 causes of death worldwide. New biomarker-based serodiagnostics and vaccines are unmet needs stalling disease control. Antigen 60 (A60) is a thermostable mycobacterial complex typically purified from Bacillus Calmette-Guérin (BCG) vaccine. A60 was historically evaluated for TB serodiagnostic and vaccine potential with variable findings. Despite containing immunogenic proteins, A60 has yet to be proteomically characterized. Here, commercial A60 was (1) trypsin-digested in-solution, analyzed by LC-MS/MS, searched against M. tuberculosis H37Rv and M. bovis BCG Uniprot databases; (2) analyzed using STRING to predict protein–protein interactions; and (3) probed with anti-TB monoclonal antibodies and patient immunoglobulin G (IgG) on Western blot to evaluate antigenicity. We detected 778 proteins in two A60 samples (440 proteins shared), including DnaK, LprG, LpqH, and GroEL1/2, reportedly present in mycobacterial extracellular vesicles (EV). Of these, 107 were also reported in EVs of M. tuberculosis, and 27 key proteins had significant protein–protein interaction, with clustering for chaperonins, ribosomal proteins, and proteins for ligand transport (LpqH and LprG). On Western blot, 7/8 TB and 1/8 non-TB sera samples had reactivity against 37–50 kDa proteins, while LpqH, GroEL2, and PstS1 were strongly detected. In conclusion, A60 comprises numerous proteins, including EV proteins, with predicted biological interactions, which may have implications on biomarker and vaccine development.

scholarly journals Distinct Expression and Methylation Patterns for Genes with Different Fates following a Single Whole-Genome Duplication in Flowering Plants

2020 ◽  
Vol 37 (8) ◽  
pp. 2394-2413 ◽  
Author(s):  
Tao Shi ◽  
Razgar Seyed Rahmani ◽  
Paul F Gugger ◽  
Muhua Wang ◽  
Hui Li ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Flowering Plants ◽  
Expression Level ◽  
Small Scale ◽  
Whole Genome ◽  
Functional Constraints ◽  
Expression Divergence ◽  
Protein Protein Interactions ◽  
Methylation Patterns ◽  
The Impact

Abstract For most sequenced flowering plants, multiple whole-genome duplications (WGDs) are found. Duplicated genes following WGD often have different fates that can quickly disappear again, be retained for long(er) periods, or subsequently undergo small-scale duplications. However, how different expression, epigenetic regulation, and functional constraints are associated with these different gene fates following a WGD still requires further investigation due to successive WGDs in angiosperms complicating the gene trajectories. In this study, we investigate lotus (Nelumbo nucifera), an angiosperm with a single WGD during the K–pg boundary. Based on improved intraspecific-synteny identification by a chromosome-level assembly, transcriptome, and bisulfite sequencing, we explore not only the fundamental distinctions in genomic features, expression, and methylation patterns of genes with different fates after a WGD but also the factors that shape post-WGD expression divergence and expression bias between duplicates. We found that after a WGD genes that returned to single copies show the highest levels and breadth of expression, gene body methylation, and intron numbers, whereas the long-retained duplicates exhibit the highest degrees of protein–protein interactions and protein lengths and the lowest methylation in gene flanking regions. For those long-retained duplicate pairs, the degree of expression divergence correlates with their sequence divergence, degree in protein–protein interactions, and expression level, whereas their biases in expression level reflecting subgenome dominance are associated with the bias of subgenome fractionation. Overall, our study on the paleopolyploid nature of lotus highlights the impact of different functional constraints on gene fate and duplicate divergence following a single WGD in plant.

Protein-Protein Interactions (PPI) via Deep Neural Network (DNN)

2022 ◽  
pp. 154-176
Author(s):  
Zizhe Gao ◽  
Hao Lin
Keyword(s):  
Neural Network ◽  
Protein Interactions ◽  
Rapid Development ◽  
Biological Research ◽  
Data Sets ◽  
Biological Interactions ◽  
Protein Protein Interactions ◽  
H Pylori ◽  
The Impact ◽  
Significant Health

Entering the 21st century, computer science and biological research have entered a stage of rapid development. With the rapid inflow of capital into the field of significant health research, a large number of scholars and investors have begun to focus on the impact of neural network science on biometrics, especially the study of biological interactions. With the rapid development of computer technology, scientists improve or perfect traditional experimental methods. This chapter aims to prove the reliability of the methodology and computing algorithms developed by Satyajit Mahapatra and Ivek Raj Gupta's project team. In this chapter, three datasets take the responsibility to testify the computing algorithms, and they are S. cerevisiae, H. pylori, and Human-B. Anthracis. Among these three sets of data, the S. cerevisiae is the core subset. The result shows 87%, 87.5%, and 89% accuracy and 87%, 86%, and 87% precision for these three data sets, respectively.

An efficient transient assays system using Agrobacterium-mediated transformation of onion (Allium cepa) epidermal cells

2020 ◽  
Vol 80 (03) ◽  
Author(s):  
Yu-Miao Zhang ◽  
Jun Wang ◽  
Tao Wu
Keyword(s):  
Subcellular Localization ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Epidermal Cells ◽  
Cyclin Dependent Kinase ◽  
Protein Subcellular Localization ◽  
Protein Protein Interactions ◽  
Efficient System ◽  
Protein Protein Interaction ◽  
Onion Epidermal Cells

In this study, the Agrobacterium infection medium, infection duration, detergent, and cell density were optimized. The sorghum-based infection medium (SbIM), 10-20 min infection time, addition of 0.01% Silwet L-77, and Agrobacterium optical density at 600 nm (OD600), improved the competence of onion epidermal cells to support Agrobacterium infection at >90% efficiency. Cyclin-dependent kinase D-2 (CDKD-2) and cytochrome c-type biogenesis protein (CYCH), protein-protein interactions were localized. The optimized procedure is a quick and efficient system for examining protein subcellular localization and protein-protein interaction.

Decoding Protein-protein Interactions: An Overview

2020 ◽  
Vol 20 (10) ◽  
pp. 855-882
Author(s):  
Olivia Slater ◽  
Bethany Miller ◽  
Maria Kontoyianni
Keyword(s):  
Drug Discovery ◽  
Protein Interactions ◽  
Drug Repurposing ◽  
Protein Docking ◽  
Target Space ◽  
Protein Protein Interactions ◽  
X Ray Crystallography ◽  
Protein Protein Interaction ◽  
Interaction Sites ◽  
Long Time

Drug discovery has focused on the paradigm “one drug, one target” for a long time. However, small molecules can act at multiple macromolecular targets, which serves as the basis for drug repurposing. In an effort to expand the target space, and given advances in X-ray crystallography, protein-protein interactions have become an emerging focus area of drug discovery enterprises. Proteins interact with other biomolecules and it is this intricate network of interactions that determines the behavior of the system and its biological processes. In this review, we briefly discuss networks in disease, followed by computational methods for protein-protein complex prediction. Computational methodologies and techniques employed towards objectives such as protein-protein docking, protein-protein interactions, and interface predictions are described extensively. Docking aims at producing a complex between proteins, while interface predictions identify a subset of residues on one protein that could interact with a partner, and protein-protein interaction sites address whether two proteins interact. In addition, approaches to predict hot spots and binding sites are presented along with a representative example of our internal project on the chemokine CXC receptor 3 B-isoform and predictive modeling with IP10 and PF4.

scholarly journals Short loop functional commonality identified in leukaemia proteome highlights crucial protein sub-networks

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Sun Sook Chung ◽  
Joseph C F Ng ◽  
Anna Laddach ◽  
N Shaun B Thomas ◽  
Franca Fraternali
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Interaction Network ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Short Loop ◽  
New Strategy ◽  
Loop Network ◽  
Protein Protein Interaction Network

Abstract Direct drug targeting of mutated proteins in cancer is not always possible and efficacy can be nullified by compensating protein–protein interactions (PPIs). Here, we establish an in silico pipeline to identify specific PPI sub-networks containing mutated proteins as potential targets, which we apply to mutation data of four different leukaemias. Our method is based on extracting cyclic interactions of a small number of proteins topologically and functionally linked in the Protein–Protein Interaction Network (PPIN), which we call short loop network motifs (SLM). We uncover a new property of PPINs named ‘short loop commonality’ to measure indirect PPIs occurring via common SLM interactions. This detects ‘modules’ of PPI networks enriched with annotated biological functions of proteins containing mutation hotspots, exemplified by FLT3 and other receptor tyrosine kinase proteins. We further identify functional dependency or mutual exclusivity of short loop commonality pairs in large-scale cellular CRISPR–Cas9 knockout screening data. Our pipeline provides a new strategy for identifying new therapeutic targets for drug discovery.

scholarly journals The Protein Interactome of Glycolysis in Escherichia coli

Proteomes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 16
Author(s):  
Shomeek Chowdhury ◽  
Stephen Hepper ◽  
Mudassir K. Lodi ◽  
Milton H. Saier ◽  
Peter Uetz
Keyword(s):  
Escherichia Coli ◽  
Protein Interactions ◽  
Allosteric Regulation ◽  
Glycolytic Enzymes ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Interacting Protein ◽  
E Coli ◽  
Protein Interactome ◽  
The Impact

Glycolysis is regulated by numerous mechanisms including allosteric regulation, post-translational modification or protein-protein interactions (PPI). While glycolytic enzymes have been found to interact with hundreds of proteins, the impact of only some of these PPIs on glycolysis is well understood. Here we investigate which of these interactions may affect glycolysis in E. coli and possibly across numerous other bacteria, based on the stoichiometry of interacting protein pairs (from proteomic studies) and their conservation across bacteria. We present a list of 339 protein-protein interactions involving glycolytic enzymes but predict that ~70% of glycolytic interactors are not present in adequate amounts to have a significant impact on glycolysis. Finally, we identify a conserved but uncharacterized subset of interactions that are likely to affect glycolysis and deserve further study.

scholarly journals Universal Screening Methods and Applications of ThermoFluor®

2006 ◽  
Vol 11 (7) ◽  
pp. 854-863 ◽  
Author(s):  
Maxwell D. Cummings ◽  
Michael A. Farnum ◽  
Marina I. Nelen
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Protein Unfolding ◽  
Direct Detection ◽  
Functional Characterization ◽  
Screening Methods ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Bacterial Enzyme ◽  
Research Problems

The genomics revolution has unveiled a wealth of poorly characterized proteins. Scientists are often able to produce milligram quantities of proteins for which function is unknown or hypothetical, based only on very distant sequence homology. Broadly applicable tools for functional characterization are essential to the illumination of these orphan proteins. An additional challenge is the direct detection of inhibitors of protein-protein interactions (and allosteric effectors). Both of these research problems are relevant to, among other things, the challenge of finding and validating new protein targets for drug action. Screening collections of small molecules has long been used in the pharmaceutical industry as 1 method of discovering drug leads. Screening in this context typically involves a function-based assay. Given a sufficient quantity of a protein of interest, significant effort may still be required for functional characterization, assay development, and assay configuration for screening. Increasingly, techniques are being reported that facilitate screening for specific ligands for a protein of unknown function. Such techniques also allow for function-independent screening with better characterized proteins. ThermoFluor®, a screening instrument based on monitoring ligand effects on temperature-dependent protein unfolding, can be applied when protein function is unknown. This technology has proven useful in the decryption of an essential bacterial enzyme and in the discovery of a series of inhibitors of a cancer-related, protein-protein interaction. The authors review some of the tools relevant to these research problems in drug discovery, and describe our experiences with 2 different proteins.

scholarly journals Trifunctional cross-linker for mapping protein-protein interaction networks and comparing protein conformational states

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Dan Tan ◽  
Qiang Li ◽  
Mei-Jun Zhang ◽  
Chao Liu ◽  
Chengying Ma ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Structural Information ◽  
Affinity Purification ◽  
Protein Protein Interactions ◽  
C Elegans ◽  
Protein Protein Interaction ◽  
Lysine Residues ◽  
Spacer Arm ◽  
Cross Linker ◽  
Protein Nucleic Acid

To improve chemical cross-linking of proteins coupled with mass spectrometry (CXMS), we developed a lysine-targeted enrichable cross-linker containing a biotin tag for affinity purification, a chemical cleavage site to separate cross-linked peptides away from biotin after enrichment, and a spacer arm that can be labeled with stable isotopes for quantitation. By locating the flexible proteins on the surface of 70S ribosome, we show that this trifunctional cross-linker is effective at attaining structural information not easily attainable by crystallography and electron microscopy. From a crude Rrp46 immunoprecipitate, it helped identify two direct binding partners of Rrp46 and 15 protein-protein interactions (PPIs) among the co-immunoprecipitated exosome subunits. Applying it to E. coli and C. elegans lysates, we identified 3130 and 893 inter-linked lysine pairs, representing 677 and 121 PPIs. Using a quantitative CXMS workflow we demonstrate that it can reveal changes in the reactivity of lysine residues due to protein-nucleic acid interaction.

Swim-exercised mice show a decreased level of protein O-GlcNAcylation and expression of O-GlcNAc transferase in heart

2011 ◽  
Vol 111 (1) ◽  
pp. 157-162 ◽  
Author(s):  
Darrell D. Belke
Keyword(s):  
Protein Interactions ◽  
Contractile Function ◽  
Cell Physiology ◽  
Protein Protein Interactions ◽  
Training Exercise ◽  
General Protein ◽  
Exercise Induced ◽  
Glcnac Transferase ◽  
The Impact ◽  
Physiological Hypertrophy

Swim-training exercise in mice leads to cardiac remodeling associated with an improvement in contractile function. Protein O-linked N-acetylglucosamine ( O-GlcNAcylation) is a posttranslational modification of serine and threonine residues capable of altering protein-protein interactions affecting gene transcription, cell signaling pathways, and general cell physiology. Increased levels of protein O-GlcNAcylation in the heart have been associated with pathological conditions such as diabetes, ischemia, and hypertrophic heart failure. In contrast, the impact of physiological exercise on protein O-GlcNAcylation in the heart is currently unknown. Swim-training exercise in mice was associated with the development of a physiological hypertrophy characterized by an improvement in contractile function relative to sedentary mice. General protein O-GlcNAcylation was significantly decreased in swim-exercised mice. This effect was mirrored in the level of O-GlcNAcylation of individual proteins such as SP1. The decrease in protein O-GlcNAcylation was associated with a decrease in the expression of O-GlcNAc transferase (OGT) and glutamine-fructose amidotransferase (GFAT) 2 mRNA. O-GlcNAcase (OGA) activity was actually lower in swim-trained than sedentary hearts, suggesting that it did not contribute to the decreased protein O-GlcNAcylation. Thus it appears that exercise-induced physiological hypertrophy is associated with a decrease in protein O-GlcNAcylation, which could potentially contribute to changes in gene expression and other physiological changes associated with exercise.

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