The Impact of Structural Proteomics on the Prediction of Protein– Protein Interactions

2008 ◽  
pp. 251-267
Author(s):  
Christina Kiel ◽  
Luis Serrano
Keyword(s):  
Protein Interactions ◽  
Structural Proteomics ◽  
Protein Protein Interactions ◽  
The Impact

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.

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.

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 Subcellular Targeting of Plant Sucrose Transporters Is Affected by Their Oligomeric State

Plants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 158 ◽  
Author(s):  
Varsha Garg ◽  
Aleksandra Hackel ◽  
Christina Kühn
Keyword(s):  
Protein Interactions ◽  
Subcellular Distribution ◽  
Sucrose Transporter ◽  
Membrane Microdomains ◽  
Protein Protein Interactions ◽  
Subcellular Targeting ◽  
Oligomeric State ◽  
Sucrose Transporters ◽  
Interaction Partners ◽  
The Impact

Post-translational regulation of sucrose transporters represents one possibility to adapt transporter activity in a very short time frame. This can occur either via phosphorylation/dephosphorylation, oligomerization, protein–protein interactions, endocytosis/exocytosis, or degradation. It is also known that StSUT1 can change its compartmentalization at the plasma membrane and concentrate in membrane microdomains in response to changing redox conditions. A systematic screen for protein–protein-interactions of plant sucrose transporters revealed that the interactome of all three known sucrose transporters from the Solanaceous species Solanum tuberosum and Solanum lycopersicum represents a specific subset of interaction partners, suggesting different functions for the three different sucrose transporters. Here, we focus on factors that affect the subcellular distribution of the transporters. It was already known that sucrose transporters are able to form homo- as well as heterodimers. Here, we reveal the consequences of homo- and heterodimer formation and the fact that the responses of individual sucrose transporters will respond differently. Sucrose transporter SlSUT2 is mainly found in intracellular vesicles and several of its interaction partners are involved in vesicle traffic and subcellular targeting. The impact of interaction partners such as SNARE/VAMP proteins on the localization of SlSUT2 protein will be investigated, as well as the impact of inhibitors, excess of substrate, or divalent cations which are known to inhibit SUT1-mediated sucrose transport in yeast cells. Thereby we are able to identify factors regulating sucrose transporter activity via a change of their subcellular distribution.

scholarly journals Activities and regulation of peptidoglycan synthases

2015 ◽  
Vol 370 (1679) ◽  
pp. 20150031 ◽  
Author(s):  
Alexander J. F. Egan ◽  
Jacob Biboy ◽  
Inge van't Veer ◽  
Eefjan Breukink ◽  
Waldemar Vollmer
Keyword(s):  
Escherichia Coli ◽  
Protein Interactions ◽  
Cytoplasmic Membrane ◽  
Current Knowledge ◽  
Protein Protein Interactions ◽  
Penicillin Binding Proteins ◽  
Multiple Protein ◽  
Cell Division Protein ◽  
The Impact

Peptidoglycan (PG) is an essential component in the cell wall of nearly all bacteria, forming a continuous, mesh-like structure, called the sacculus, around the cytoplasmic membrane to protect the cell from bursting by its turgor. Although PG synthases, the penicillin-binding proteins (PBPs), have been studied for 70 years, useful in vitro assays for measuring their activities were established only recently, and these provided the first insights into the regulation of these enzymes. Here, we review the current knowledge on the glycosyltransferase and transpeptidase activities of PG synthases. We provide new data showing that the bifunctional PBP1A and PBP1B from Escherichia coli are active upon reconstitution into the membrane environment of proteoliposomes, and that these enzymes also exhibit DD-carboxypeptidase activity in certain conditions. Both novel features are relevant for their functioning within the cell. We also review recent data on the impact of protein–protein interactions and other factors on the activities of PBPs. As an example, we demonstrate a synergistic effect of multiple protein–protein interactions on the glycosyltransferase activity of PBP1B, by its cognate lipoprotein activator LpoB and the essential cell division protein FtsN.

scholarly journals Expression attenuation as a mechanism of robustness against gene duplication

2021 ◽  
Vol 118 (6) ◽  
pp. e2014345118
Author(s):  
Diana Ascencio ◽  
Guillaume Diss ◽  
Isabelle Gagnon-Arsenault ◽  
Alexandre K. Dubé ◽  
Alexander DeLuna ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Protein Interactions ◽  
Protein Complexes ◽  
Phenotypic Diversity ◽  
26S Proteasome ◽  
Gene Duplications ◽  
Protein Protein Interactions ◽  
Individual Gene ◽  
The Impact

Gene duplication is ubiquitous and a major driver of phenotypic diversity across the tree of life, but its immediate consequences are not fully understood. Deleterious effects would decrease the probability of retention of duplicates and prevent their contribution to long-term evolution. One possible detrimental effect of duplication is the perturbation of the stoichiometry of protein complexes. Here, we measured the fitness effects of the duplication of 899 essential genes in the budding yeast using high-resolution competition assays. At least 10% of genes caused a fitness disadvantage when duplicated. Intriguingly, the duplication of most protein complex subunits had small to nondetectable effects on fitness, with few exceptions. We selected four complexes with subunits that had an impact on fitness when duplicated and measured the impact of individual gene duplications on their protein–protein interactions. We found that very few duplications affect both fitness and interactions. Furthermore, large complexes such as the 26S proteasome are protected from gene duplication by attenuation of protein abundance. Regulatory mechanisms that maintain the stoichiometric balance of protein complexes may protect from the immediate effects of gene duplication. Our results show that a better understanding of protein regulation and assembly in complexes is required for the refinement of current models of gene duplication.

scholarly journals Proteomics of Cryptococcus neoformans: From the Lab to the Clinic

2021 ◽  
Vol 22 (22) ◽  
pp. 12390
Author(s):  
Ben Muselius ◽  
Shay-Lynn Durand ◽  
Jennifer Geddes-McAlister
Keyword(s):  
Cryptococcus Neoformans ◽  
Protein Interactions ◽  
Fungal Pathogen ◽  
Fungal Pathogens ◽  
Severe Disease ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Protein Protein Interactions ◽  
Dynamic Relationship ◽  
The Impact

Fungal pathogens cause an array of diseases by targeting both immunocompromised and immunocompetent hosts. Fungi overcome our current arsenal of antifungals through the emergence and evolution of resistance. In particular, the human fungal pathogen, Cryptococcus neoformans is found ubiquitously within the environment and causes severe disease in immunocompromised individuals around the globe with limited treatment options available. To uncover fundamental knowledge about this fungal pathogen, as well as investigate new detection and treatment strategies, mass spectrometry-based proteomics provides a plethora of tools and applications, as well as bioinformatics platforms. In this review, we highlight proteomics approaches within the laboratory to investigate changes in the cellular proteome, secretome, and extracellular vesicles. We also explore regulation by post-translational modifications and the impact of protein–protein interactions. Further, we present the development and comprehensive assessment of murine models of cryptococcal infection, which provide valuable tools to define the dynamic relationship between the host and pathogen during disease. Finally, we explore recent quantitative proteomics studies that begin to extrapolate the findings from the bench to the clinic for improved methods of fungal detection and monitoring. Such studies support a framework for personalized medical approaches to eradicate diseases caused by C. neoformans.

scholarly journals ROLE OF THE NOTCH1 GENE IN FORMATION OF AORTIC ANEURYSM

2018 ◽  
pp. 53-59
Author(s):  
O. V. Irtyuga ◽  
O. A. Freilichman ◽  
D. S. Krivonosov ◽  
A. B. Malashicheva ◽  
S. I. Tarnovskaya ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Direct Sequencing ◽  
Mutation Screening ◽  
Protein Protein Interactions ◽  
Highly Pathogenic ◽  
Targeted Mutation ◽  
Aortic Pathology ◽  
Inborn Defects ◽  
The Impact ◽  
Inborn Defect

Aim. To evaluate the impact of genetics in development of thoracic aneurysm in patients with tricuspid valve (TAV) and bicuspid aortic valve (BAV) based on the analysis and search for mutations in NOTCH1.Material and methods. In the study, 60 patients included with the dilation of thoracic aorta more than 40 mm and 200 patients with no aortic pathology, included in the comparison group. All patients underwent echocardiographic assessment on Vivid 7 (GE, USA) equipment, by standard protocol. For molecular genetics we utilized the strategy of targeted mutation screening, including the analysis of 10 of 34 exones of the gene NOTCH1, performed with the direct sequencing.Results. Patients with BAV were younger than those with no inborn defect. Arterial hypertension was verified only in every second BAV patient. Also, maximal rates of blood pressure were significantly lower in patients with inborn defects (р<0,02). As a result of genetic analysis in the studied group, in 9 patients with inborn defect and 2 patients with TAV there were 10 variants found of aminoacid replacement in 6 among 10 analyzed exones, of those 5 replacements — synonimic, and the mutation S2449R was found first time. Mutations P1227S, E1305K, R1279H and D1267N were found at the site of Notch1 protein binding with DLL4, of those 3 are highly pathogenic, that could influence the protein-protein interactions Notch1 with DLL4 leading to formation on aneurysm.Conclusion. Mutations P1227S D1267, E1305K in the gene NOTCH1, being highly pathogenic, may lead to the changes of protein functioning via Notch signalling disorder, that is more characteristic for BAV patients.

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.

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