scholarly journals The analysis of participation of individual proteins in the protein interactome formation

2018 ◽  
Vol 64 (2) ◽  
pp. 169-174 ◽  
Author(s):  
A.V. Florinskaya ◽  
P.V. Ershov ◽  
Y.V. Mezentsev ◽  
L.A. Kaluzhskiy ◽  
E.O. Yablokov ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Gel Filtration ◽  
Protein Protein Interactions ◽  
Systemic Analysis ◽  
Protein Interactome ◽  
Molecular Masses ◽  
Monomeric Proteins ◽  
Average Molecular Masses ◽  
Mixed Protein

It becomes increasingly clear that most proteins of living systems exist as components of various protein complexes rather than individual molecules. The use of various proteomic techniques significantly extended our knowledge not only about functioning of individual complexes but also formed a basis for systemic analysis of protein-protein interactions. In this study gel-filtration chromatography accompanied by mass-spectrometry was used for the interactome analysis of human liver proteins. In six fractions (with average molecular masses of 45 kDa, 60 kDa, 85 kDa, 150 kDa, 250 kDa, and 440 kDa) 797 proteins were identified. In dependence of their distribution profiles in the fractions, these proteins could be subdivided into four groups: (1) single monomeric proteins that are not involved in formation of stable protein complexes; (2) proteins existing as homodimers or heterodimers with comparable partners; (3) proteins that are partially exist as monomers and partially as components of protein complexes; (4) proteins that do not exist in the monomolecular state, but also exist within protein complexes containing three or more subunits. Application of this approach to known isatin-binding proteins resulted in identification of proteins involved in formation of the homo- and heterodimers and mixed protein complexes.

scholarly journals Conserved Central Intraviral Protein Interactome of the Herpesviridae Family

mSystems ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Anna Hernández Durán ◽  
Kay Grünewald ◽  
Maya Topf
Keyword(s):  
Protein Interactions ◽  
Computational Models ◽  
Functional Organization ◽  
Driving Forces ◽  
Protein Complexes ◽  
Structural Features ◽  
System Level ◽  
Protein Protein Interactions ◽  
Protein Interactome ◽  
Essential Components

ABSTRACT Protein interactions are major driving forces behind the functional phenotypes of biological processes. As such, evolutionary footprints are reflected in system-level collections of protein-protein interactions (PPIs), i.e., protein interactomes. We conducted a comparative analysis of intraviral protein interactomes for representative species of each of the three subfamilies of herpesviruses (herpes simplex virus 1, human cytomegalovirus, and Epstein-Barr virus), which are highly prevalent etiologic agents of important human diseases. The intraviral interactomes were reconstructed by combining experimentally supported and computationally predicted protein-protein interactions. Using cross-species network comparison, we then identified family-wise conserved interactions and protein complexes, which we defined as a herpesviral “central” intraviral protein interactome. A large number of widely accepted conserved herpesviral protein complexes are present in this central intraviral interactome, encouragingly supporting the biological coherence of our results. Importantly, these protein complexes represent most, if not all, of the essential steps required during a productive life cycle. Hence the central intraviral protein interactome could plausibly represent a minimal infectious interactome of the herpesvirus family across a variety of hosts. Our data, which have been integrated into our herpesvirus interactomics database, HVint2.0, could assist in creating comprehensive system-level computational models of this viral lineage. IMPORTANCE Herpesviruses are an important socioeconomic burden for both humans and livestock. Throughout their long evolutionary history, individual herpesvirus species have developed remarkable host specificity, while collectively the Herpesviridae family has evolved to infect a large variety of eukaryotic hosts. The development of approaches to fight herpesvirus infections has been hampered by the complexity of herpesviruses’ genomes, proteomes, and structural features. The data and insights generated by our study add to the understanding of the functional organization of herpesvirus-encoded proteins, specifically of family-wise conserved features defining essential components required for a productive infectious cycle across different hosts, which can contribute toward the conceptualization of antiherpetic infection strategies with an effect on a broader range of target species. All of the generated data have been made freely available through our HVint2.0 database, a dedicated resource of curated herpesvirus interactomics purposely created to promote and assist future studies in the field.

scholarly journals Recent advances in large-scale protein interactome mapping

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 782 ◽  
Author(s):  
Virja Mehta ◽  
Laura Trinkle-Mulcahy
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Protein Complexes ◽  
Specific Protein ◽  
Quality Data ◽  
Protein Protein Interactions ◽  
Cellular Functions ◽  
Biological Studies ◽  
Protein Interactome ◽  
Literature Curation

Protein-protein interactions (PPIs) underlie most, if not all, cellular functions. The comprehensive mapping of these complex networks of stable and transient associations thus remains a key goal, both for systems biology-based initiatives (where it can be combined with other ‘omics’ data to gain a better understanding of functional pathways and networks) and for focused biological studies. Despite the significant challenges of such an undertaking, major strides have been made over the past few years. They include improvements in the computation prediction of PPIs and the literature curation of low-throughput studies of specific protein complexes, but also an increase in the deposition of high-quality data from non-biased high-throughput experimental PPI mapping strategies into publicly available databases.

Mapping of Protein-Protein Interactions: Web-Based Resources for Revealing Interactomes

2019 ◽  
Vol 26 (21) ◽  
pp. 3890-3910 ◽  
Author(s):  
Branislava Gemovic ◽  
Neven Sumonja ◽  
Radoslav Davidovic ◽  
Vladimir Perovic ◽  
Nevena Veljkovic
Keyword(s):  
Drug Discovery ◽  
Protein Interactions ◽  
Protein Complexes ◽  
Experimental Studies ◽  
Protein Protein Interactions ◽  
Web Based ◽  
Prediction Tools ◽  
Physiological Processes ◽  
Modern Drug ◽  
Ppi Prediction

Background: The significant number of protein-protein interactions (PPIs) discovered by harnessing concomitant advances in the fields of sequencing, crystallography, spectrometry and two-hybrid screening suggests astonishing prospects for remodelling drug discovery. The PPI space which includes up to 650 000 entities is a remarkable reservoir of potential therapeutic targets for every human disease. In order to allow modern drug discovery programs to leverage this, we should be able to discern complete PPI maps associated with a specific disorder and corresponding normal physiology. Objective: Here, we will review community available computational programs for predicting PPIs and web-based resources for storing experimentally annotated interactions. Methods: We compared the capacities of prediction tools: iLoops, Struck2Net, HOMCOS, COTH, PrePPI, InterPreTS and PRISM to predict recently discovered protein interactions. Results: We described sequence-based and structure-based PPI prediction tools and addressed their peculiarities. Additionally, since the usefulness of prediction algorithms critically depends on the quality and quantity of the experimental data they are built on; we extensively discussed community resources for protein interactions. We focused on the active and recently updated primary and secondary PPI databases, repositories specialized to the subject or species, as well as databases that include both experimental and predicted PPIs. Conclusion: PPI complexes are the basis of important physiological processes and therefore, possible targets for cell-penetrating ligands. Reliable computational PPI predictions can speed up new target discoveries through prioritization of therapeutically relevant protein–protein complexes for experimental studies.

Protein Interaction Domains and Post-Translational Modifications: Structural Features and Drug Discovery Applications

2020 ◽  
Vol 27 (37) ◽  
pp. 6306-6355 ◽  
Author(s):  
Marian Vincenzi ◽  
Flavia Anna Mercurio ◽  
Marilisa Leone
Keyword(s):  
Drug Discovery ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Structural Information ◽  
Protein Complexes ◽  
Structural Features ◽  
Protein Protein Interactions ◽  
Modular Architecture ◽  
Post Translational Modifications ◽  
Interaction Domains

Background:: Many pathways regarding healthy cells and/or linked to diseases onset and progression depend on large assemblies including multi-protein complexes. Protein-protein interactions may occur through a vast array of modules known as protein interaction domains (PIDs). Objective:: This review concerns with PIDs recognizing post-translationally modified peptide sequences and intends to provide the scientific community with state of art knowledge on their 3D structures, binding topologies and potential applications in the drug discovery field. Method:: Several databases, such as the Pfam (Protein family), the SMART (Simple Modular Architecture Research Tool) and the PDB (Protein Data Bank), were searched to look for different domain families and gain structural information on protein complexes in which particular PIDs are involved. Recent literature on PIDs and related drug discovery campaigns was retrieved through Pubmed and analyzed. Results and Conclusion:: PIDs are rather versatile as concerning their binding preferences. Many of them recognize specifically only determined amino acid stretches with post-translational modifications, a few others are able to interact with several post-translationally modified sequences or with unmodified ones. Many PIDs can be linked to different diseases including cancer. The tremendous amount of available structural data led to the structure-based design of several molecules targeting protein-protein interactions mediated by PIDs, including peptides, peptidomimetics and small compounds. More studies are needed to fully role out, among different families, PIDs that can be considered reliable therapeutic targets, however, attacking PIDs rather than catalytic domains of a particular protein may represent a route to obtain selective inhibitors.

scholarly journals Frequent assembly of chimeric complexes in the protein interaction network of an interspecies yeast hybrid

2020 ◽  
Author(s):  
Rohan Dandage ◽  
Caroline M Berger ◽  
Isabelle Gagnon-Arsenault ◽  
Kyung-Mee Moon ◽  
Richard Greg Stacey ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Molecular Level ◽  
Yeast Species ◽  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Chimeric Protein ◽  
Interaction Network ◽  
Protein Protein Interactions ◽  
Extreme Phenotypes ◽  
Yeast Hybrid

Abstract Hybrids between species often show extreme phenotypes, including some that take place at the molecular level. In this study, we investigated the phenotypes of an interspecies diploid hybrid in terms of protein-protein interactions inferred from protein correlation profiling. We used two yeast species, Saccharomyces cerevisiae and Saccharomyces uvarum, which are interfertile, but yet have proteins diverged enough to be differentiated using mass spectrometry. Most of the protein-protein interactions are similar between hybrid and parents, and are consistent with the assembly of chimeric complexes, which we validated using an orthogonal approach for the prefoldin complex. We also identified instances of altered protein-protein interactions in the hybrid, for instance in complexes related to proteostasis and in mitochondrial protein complexes. Overall, this study uncovers the likely frequent occurrence of chimeric protein complexes with few exceptions, which may result from incompatibilities or imbalances between the parental proteins.

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 Mass spectrometry-based cross-linking study shows that the Psb28 protein binds to cytochrome b559 in Photosystem II

2017 ◽  
Vol 114 (9) ◽  
pp. 2224-2229 ◽  
Author(s):  
Daniel A. Weisz ◽  
Haijun Liu ◽  
Hao Zhang ◽  
Sundarapandian Thangapandian ◽  
Emad Tajkhorshid ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Photosystem Ii ◽  
Protein Interactions ◽  
Protein Complexes ◽  
Protein Docking ◽  
Cross Linking ◽  
Protein Protein Interactions ◽  
Cytochrome B559 ◽  
Reaction Center Complex ◽  
Assembly Intermediate

Photosystem II (PSII), a large pigment protein complex, undergoes rapid turnover under natural conditions. During assembly of PSII, oxidative damage to vulnerable assembly intermediate complexes must be prevented. Psb28, the only cytoplasmic extrinsic protein in PSII, protects the RC47 assembly intermediate of PSII and assists its efficient conversion into functional PSII. Its role is particularly important under stress conditions when PSII damage occurs frequently. Psb28 is not found, however, in any PSII crystal structure, and its structural location has remained unknown. In this study, we used chemical cross-linking combined with mass spectrometry to capture the transient interaction of Psb28 with PSII. We detected three cross-links between Psb28 and the α- and β-subunits of cytochrome b559, an essential component of the PSII reaction-center complex. These distance restraints enable us to position Psb28 on the cytosolic surface of PSII directly above cytochrome b559, in close proximity to the QB site. Protein–protein docking results also support Psb28 binding in this region. Determination of the Psb28 binding site and other biochemical evidence allow us to propose a mechanism by which Psb28 exerts its protective effect on the RC47 intermediate. This study also shows that isotope-encoded cross-linking with the “mass tags” selection criteria allows confident identification of more cross-linked peptides in PSII than has been previously reported. This approach thus holds promise to identify other transient protein–protein interactions in membrane protein complexes.

Metallocluster transactions: dynamic protein interactions guide the biosynthesis of Fe–S clusters in bacteria

2018 ◽  
Vol 46 (6) ◽  
pp. 1593-1603 ◽  
Author(s):  
Chenkang Zheng ◽  
Patricia C. Dos Santos
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Specific Protein ◽  
Biological Synthesis ◽  
Cluster Assembly ◽  
Sequence Motifs ◽  
Protein Protein Interactions ◽  
Cysteine Desulfurase ◽  
Wide Range ◽  
Domains Of Life

Iron–sulfur (Fe–S) clusters are ubiquitous cofactors present in all domains of life. The chemistries catalyzed by these inorganic cofactors are diverse and their associated enzymes are involved in many cellular processes. Despite the wide range of structures reported for Fe–S clusters inserted into proteins, the biological synthesis of all Fe–S clusters starts with the assembly of simple units of 2Fe–2S and 4Fe–4S clusters. Several systems have been associated with the formation of Fe–S clusters in bacteria with varying phylogenetic origins and number of biosynthetic and regulatory components. All systems, however, construct Fe–S clusters through a similar biosynthetic scheme involving three main steps: (1) sulfur activation by a cysteine desulfurase, (2) cluster assembly by a scaffold protein, and (3) guided delivery of Fe–S units to either final acceptors or biosynthetic enzymes involved in the formation of complex metalloclusters. Another unifying feature on the biological formation of Fe–S clusters in bacteria is that these systems are tightly regulated by a network of protein interactions. Thus, the formation of transient protein complexes among biosynthetic components allows for the direct transfer of reactive sulfur and Fe–S intermediates preventing oxygen damage and reactions with non-physiological targets. Recent studies revealed the importance of reciprocal signature sequence motifs that enable specific protein–protein interactions and consequently guide the transactions between physiological donors and acceptors. Such findings provide insights into strategies used by bacteria to regulate the flow of reactive intermediates and provide protein barcodes to uncover yet-unidentified cellular components involved in Fe–S metabolism.

scholarly journals A computational interactome and functional annotation for the human proteome

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
José Ignacio Garzón ◽  
Lei Deng ◽  
Diana Murray ◽  
Sagi Shapira ◽  
Donald Petrey ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Enrichment Analysis ◽  
Human Proteome ◽  
Gene Set Enrichment Analysis ◽  
Protein Protein Interactions ◽  
Functional Relationships ◽  
Structural Relationships ◽  
Human Proteins ◽  
Validation Tests

We present a database, PrePPI (Predicting Protein-Protein Interactions), of more than 1.35 million predicted protein-protein interactions (PPIs). Of these at least 127,000 are expected to constitute direct physical interactions although the actual number may be much larger (~500,000). The current PrePPI, which contains predicted interactions for about 85% of the human proteome, is related to an earlier version but is based on additional sources of interaction evidence and is far larger in scope. The use of structural relationships allows PrePPI to infer numerous previously unreported interactions. PrePPI has been subjected to a series of validation tests including reproducing known interactions, recapitulating multi-protein complexes, analysis of disease associated SNPs, and identifying functional relationships between interacting proteins. We show, using Gene Set Enrichment Analysis (GSEA), that predicted interaction partners can be used to annotate a protein’s function. We provide annotations for most human proteins, including many annotated as having unknown function.

scholarly journals Interfacial Peptides as Affinity Modulating Agents of Protein-Protein Interactions

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 106
Author(s):  
Pavel V. Ershov ◽  
Yuri V. Mezentsev ◽  
Alexis S. Ivanov
Keyword(s):  
Protein Interactions ◽  
Targeted Delivery ◽  
Protein Complexes ◽  
Protein Protein Interactions ◽  
Good Efficiency ◽  
Cellular Targets ◽  
Proteolytic Stability ◽  
Clinically Significant

The identification of disease-related protein-protein interactions (PPIs) creates objective conditions for their pharmacological modulation. The contact area (interfaces) of the vast majority of PPIs has some features, such as geometrical and biochemical complementarities, “hot spots”, as well as an extremely low mutation rate that give us key knowledge to influence these PPIs. Exogenous regulation of PPIs is aimed at both inhibiting the assembly and/or destabilization of protein complexes. Often, the design of such modulators is associated with some specific problems in targeted delivery, cell penetration and proteolytic stability, as well as selective binding to cellular targets. Recent progress in interfacial peptide design has been achieved in solving all these difficulties and has provided a good efficiency in preclinical models (in vitro and in vivo). The most promising peptide-containing therapeutic formulations are under investigation in clinical trials. In this review, we update the current state-of-the-art in the field of interfacial peptides as potent modulators of a number of disease-related PPIs. Over the past years, the scientific interest has been focused on following clinically significant heterodimeric PPIs MDM2/p53, PD-1/PD-L1, HIF/HIF, NRF2/KEAP1, RbAp48/MTA1, HSP90/CDC37, BIRC5/CRM1, BIRC5/XIAP, YAP/TAZ–TEAD, TWEAK/FN14, Bcl-2/Bax, YY1/AKT, CD40/CD40L and MINT2/APP.

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