scholarly journals The features of polyglutamine regions depend on their evolutionary stability

2020 ◽  
Author(s):  
Pablo Mier ◽  
Miguel A. Andrade-Navarro
Keyword(s):  
Amino Acid ◽  
Codon Usage ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Coiled Coil ◽  
Evolutionary Stability ◽  
Length Variation ◽  
Evolutionary Analysis ◽  
Protein Protein Interaction ◽  
Structural Conformation

Abstract Background: Polyglutamine regions (polyQ) are one of the most studied and prevalent homorepeats in eukaryotes. They have a particular length-dependent codon usage, which relates to a characteristic CAG-slippage mechanism. Pathologically expanded tracts of polyQ are known to form aggregates and are involved in the development of several human neurodegenerative diseases. The non-pathogenic function of polyQ is to mediate protein-protein interactions via a coiled-coil pairing with an interactor. They are usually located in a helical context. Results: Here we study the stability of polyQ regions in evolution, using a set of 60 proteomes from four distinct taxonomic groups (Insecta, Teleostei, Sauria and Mammalia). The polyQ regions can be distinctly grouped in three categories based on their evolutionary stability: stable, unstable by length variation (inserted), and unstable by mutations (mutated). PolyQ regions in these categories can be significantly distinguished by their glutamine codon usage, and we show that the CAG-slippage mechanism is predominant in inserted polyQ of Sauria and Mammalia. The polyQ amino acid context is also influenced by the polyQ stability, with a higher proportion of proline residues around inserted polyQ. By studying the secondary structure of the sequences surrounding polyQ regions, we found that regarding the structural conformation around a polyQ, its stability category is more relevant than its taxonomic information. The protein-protein interaction capacity of a polyQ is also affected by its stability, as stable polyQ have more interactors than unstable polyQ.Conclusions: Our results show that apart from the sequence of a polyQ, information about its orthologous sequences is needed to assess its function. Codon usage, amino acid context, structural conformation and the protein-protein interaction capacity of polyQ from all studied taxa critically depend on the region stability. There are however some taxa-specific polyQ features that override this importance. We conclude that a taxa-driven evolutionary analysis is of the highest importance for the comprehensive study of any feature of polyglutamine regions.

scholarly journals The features of polyglutamine regions depend on their evolutionary stability

2020 ◽  
Author(s):  
Pablo Mier ◽  
Miguel A. Andrade-Navarro
Keyword(s):  
Amino Acid ◽  
Codon Usage ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Coiled Coil ◽  
Evolutionary Stability ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Structural Conformation ◽  
Taxonomic Groups

Abstract Background Polyglutamine regions (polyQ) are one of the most studied and prevalent homorepeats in eukaryotes. They have a particular length-dependent codon usage, which relates to a characteristic CAG-slippage mechanism. Pathologically expanded tracts of polyQ are known to form aggregates and are involved in the development of several human neurodegenerative diseases. The non-pathogenic function of polyQ is to mediate protein-protein interactions via a coiled-coil pairing with an interactor. They are usually located in a helical context.Results Here we show how these known features related to polyQ depend on their stability in evolution. We have classified the polyQ regions of 60 proteomes from four distinct taxonomic groups (Insecta, Teleostei, Sauria and Mammalia) in three main categories based on their evolutionary stability. Codon usage, amino acid context, structural conformation and the protein-protein interaction capacity of polyQ from all studied taxa critically depend on the region stability.Conclusions Our results show that apart from the sequence of a polyQ, information about its orthologous sequences is needed to assess its function.

scholarly journals Co-evolution between codon usage and Protein-Protein Interaction Networks in Bacterial genomes

2020 ◽  
Author(s):  
Maddalena Dilucca ◽  
Giulio Cimini ◽  
Sergio Forcelloni ◽  
Andrea Giansanti
Keyword(s):  
Codon Usage ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Codon Bias ◽  
Gc Content ◽  
Interaction Network ◽  
Protein Interaction Networks ◽  
Bacterial Genomes ◽  
Protein Protein Interaction ◽  
Protein Protein Interaction Networks

AbstractIn this work, we study the correlation between codon usage and the network features of the PPI in bacteria genomes. We want to extend the information by Dilucca et al. (2015) about E.Coli’s genome for a set of other 34 bacteria. We use PCA techniques in the space of codon bias indices (compAI, compAI_w, tAI, NC) and GC content to show that genes with similar patterns of codon usage feature have a significantly higher probability that their encoded proteins interact within the PPI. And vice-versa, we show that interacting in the PPI have a coherent codon usage. This work could allow for future investigations into the possible effects that codon bias signal can have on the topology of protein interaction network and, as such, to improve existing bioinformatics methods for predicting protein interactions.

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.

scholarly journals Structural Glycoprotein E2 of Classical Swine Fever Virus Interacts with Host Protein Dynactin Subunit 6 (DCTN6) during the Virus Infectious Cycle

2019 ◽  
Vol 94 (1) ◽  
Author(s):  
M. V. Borca ◽  
E. A. Vuono ◽  
E. Ramirez-Medina ◽  
P. Azzinaro ◽  
K. A. Berggren ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Interaction ◽  
Hybrid Approach ◽  
Classical Swine Fever ◽  
Host Protein ◽  
Yeast Two Hybrid ◽  
Protein Protein Interaction ◽  
Viral Virulence ◽  
Glycoprotein E2 ◽  
Two Hybrid

ABSTRACT The E2 protein in classical swine fever (CSF) virus (CSFV) is the major virus structural glycoprotein and is an essential component of the viral particle. E2 has been shown to be involved in several functions, including virus adsorption, induction of protective immunity, and virulence in swine. Using the yeast two-hybrid system, we previously identified a swine host protein, dynactin subunit 6 (DCTN6) (a component of the cell dynactin complex), as a specific binding partner for E2. We confirmed the interaction between DCTN6 and E2 proteins in CSFV-infected swine cells by using two additional independent methodologies, i.e., coimmunoprecipitation and proximity ligation assays. E2 residues critical for mediating the protein-protein interaction with DCTN6 were mapped by a reverse yeast two-hybrid approach using a randomly mutated E2 library. A recombinant CSFV mutant, E2ΔDCTN6v, harboring specific substitutions in those critical residues was developed to assess the importance of the E2-DCTN6 protein-protein interaction for virus replication and virulence in swine. CSFV E2ΔDCTN6v showed reduced replication, compared with the parental virus, in an established swine cell line (SK6) and in primary swine macrophage cultures. Remarkably, animals infected with CSFV E2ΔDCTN6v remained clinically normal during the 21-day observation period, which suggests that the ability of CSFV E2 to bind host DCTN6 protein efficiently during infection may play a role in viral virulence. IMPORTANCE Structural glycoprotein E2 is an important component of CSFV due to its involvement in many virus activities, particularly virus-host interactions. Here, we present the description and characterization of the protein-protein interaction between E2 and the swine host protein DCTN6 during virus infection. The E2 amino acid residues mediating the interaction with DCTN6 were also identified. A recombinant CSFV harboring mutations disrupting the E2-DCTN6 interaction was created. The effect of disrupting the E2-DCTN6 protein-protein interaction was studied using reverse genetics. It was shown that the same amino acid substitutions that abrogated the E2-DCTN6 interaction in vitro constituted a critical factor in viral virulence in the natural host, domestic swine. This highlights the potential importance of the E2-DCTN6 protein-protein interaction in CSFV virulence and provides possible mechanisms of virus attenuation for the development of improved CSF vaccines.

scholarly journals Mutations and Protein Interaction Landscape Reveal Key Cellular Events Perturbed in Upper Motor Neurons with HSP and PLS

2021 ◽  
Vol 11 (5) ◽  
pp. 578
Author(s):  
Oge Gozutok ◽  
Benjamin Ryan Helmold ◽  
P. Hande Ozdinler
Keyword(s):  
Motor Neurons ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Cortical Neurons ◽  
Therapeutic Interventions ◽  
Functional Identification ◽  
Protein Protein Interaction ◽  
Cellular Events ◽  
Interaction Domains ◽  
Upper Motor Neurons

Hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS) are rare motor neuron diseases, which affect mostly the upper motor neurons (UMNs) in patients. The UMNs display early vulnerability and progressive degeneration, while other cortical neurons mostly remain functional. Identification of numerous mutations either directly linked or associated with HSP and PLS begins to reveal the genetic component of UMN diseases. Since each of these mutations are identified on genes that code for a protein, and because cellular functions mostly depend on protein-protein interactions, we hypothesized that the mutations detected in patients and the alterations in protein interaction domains would hold the key to unravel the underlying causes of their vulnerability. In an effort to bring a mechanistic insight, we utilized computational analyses to identify interaction partners of proteins and developed the protein-protein interaction landscape with respect to HSP and PLS. Protein-protein interaction domains, upstream regulators and canonical pathways begin to highlight key cellular events. Here we report that proteins involved in maintaining lipid homeostasis and cytoarchitectural dynamics and their interactions are of great importance for UMN health and stability. Their perturbation may result in neuronal vulnerability, and thus maintaining their balance could offer therapeutic interventions.

scholarly journals Co-evolution between codon usage and protein-protein interaction in bacteria

Gene ◽  
2021 ◽  
Vol 778 ◽  
pp. 145475
Author(s):  
Maddalena Dilucca ◽  
Giulio Cimini ◽  
Sergio Forcelloni ◽  
Andrea Giansanti
Keyword(s):  
Codon Usage ◽  
Protein Interaction ◽  
Protein Protein Interaction

Furan warheads for covalent trapping of weak protein-protein interactions: cross-linking of thymosin β4 to actin

2021 ◽  
Author(s):  
Laia Miret Casals ◽  
Willem Vannecke ◽  
Kurt Hoogewijs ◽  
Gianluca Arauz ◽  
Marina Gay ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
3D Structure ◽  
Cross Linking ◽  
Thymosin Β4 ◽  
Protein Protein Interactions ◽  
Site Specific ◽  
Protein Protein Interaction ◽  
Covalent Trapping

We describe furan as a triggerable ‘warhead’ for site-specific cross-linking using the actin and thymosin β4 (Tβ4)-complex as model of a weak and dynamic protein-protein interaction with known 3D structure...

Extracting Biological Significant Subnetworks from Protein-Protein Interactions Induced by Differentially Expressed Genes of HIV-1 Vpr Variants

2015 ◽  
Vol 4 (4) ◽  
pp. 35-51 ◽  
Author(s):  
Bandana Barman ◽  
Anirban Mukhopadhyay
Keyword(s):  
Differentially Expressed Genes ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Wild Type ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Hiv 1

Identification of protein interaction network is very important to find the cell signaling pathway for a particular disease. The authors have found the differentially expressed genes between two sample groups of HIV-1. Samples are wild type HIV-1 Vpr and HIV-1 mutant Vpr. They did statistical t-test and found false discovery rate (FDR) to identify the genes increased in expression (up-regulated) or decreased in expression (down-regulated). In the test, the authors have computed q-values of test to identify minimum FDR which occurs. As a result they found 172 differentially expressed genes between their sample wild type HIV-1 Vpr and HIV-1 mutant Vpr, R80A. They found 68 up-regulated genes and 104 down-regulated genes. From the 172 differentially expressed genes the authors found protein-protein interaction network with string-db and then clustered (subnetworks) the PPI networks with cytoscape3.0. Lastly, the authors studied significance of subnetworks with performing gene ontology and also studied the KEGG pathway of those subnetworks.

Discovering Interaction Motifs from Protein Interaction Networks

2009 ◽  
pp. 99-116 ◽  
Author(s):  
Hugo Willy
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Protein Interaction Networks ◽  
Interaction Networks ◽  
Protein Interaction Data ◽  
Interaction Data ◽  
Protein Patterns ◽  
Protein Protein Interaction ◽  
Family Based ◽  
High Throughput Experiments

Recent breakthroughs in high throughput experiments to determine protein-protein interaction have generated a vast amount of protein interaction data. However, most of the experiments could only answer the question of whether two proteins interact but not the question on the mechanisms by which proteins interact. Such understanding is crucial for understanding the protein interaction of an organism as a whole (the interactome) and even predicting novel protein interactions. Protein interaction usually occurs at some specific sites on the proteins and, given their importance, they are usually well conserved throughout the evolution of the proteins of the same family. Based on this observation, a number of works on finding protein patterns/motifs conserved in interacting proteins have emerged in the last few years. Such motifs are collectively termed as the interaction motifs. This chapter provides a review on the different approaches on finding interaction motifs with a discussion on their implications, potentials and possible areas of improvements in the future.

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