scholarly journals H2V, a Database for Human Proteins and Genes in Response to SARS-CoV-2, SARS-CoV, and MERS-CoV Infection

2020 ◽  
Author(s):  
Nan Zhou ◽  
Jinku Bao ◽  
Yuping Ning
Keyword(s):  
Differentially Expressed Genes ◽  
Protein Interactions ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Differentially Expressed ◽  
Easy Access ◽  
Differentially Expressed Proteins ◽  
Protein Protein Interactions ◽  
Associated Proteins ◽  
Human Proteins

Abstract The ongoing COVID-19 pandemic in the world is caused by SARS-CoV-2, a new coronavirus firstly discovered in the end of 2019. It has led to more than 10 million confirmed cases and more than 500,000 confirmed deaths across 216 countries by 1 July 2020, according to WHO statistics. SARS-CoV-2, SARS-CoV, and MERS-CoV are alike, killing people, impairing economy, and inflicting long-term impacts on the society. However, no specific drug or vaccine has been approved as a cure for these viruses. The efforts to develop antiviral measures are hampered by insufficient understanding of molecular responses of human to viral infections. In this study, we collected experimentally validated human proteins that interact with SARS-CoV-2 proteins, human proteins whose expression, translation and phosphorylation levels experience significantly changes after SARS-CoV-2 or SARS-CoV infection, human proteins that correlate with COVID-19 severity, and human genes whose expression levels significantly changed upon SARS-CoV-2 or MERS-CoV infection. A database, H2V, was then developed for easy access to these data. Currently H2V includes: 332 human-SARS-CoV-2 protein-protein interactions; 65 differentially expressed proteins, 232 differentially translated proteins, 1298 differentially phosphorylated proteins, 204 severity associated proteins, and 4012 differentially expressed genes responding to SARS-CoV-2 infection; 66 differentially expressed proteins responding to SARS-CoV infection; and 6981 differentially expressed genes responding to MERS-CoV infection. H2V can help to understand the cellular responses associated with SARS-CoV-2, SARS-CoV and MERS-CoV infection. It is expected to speed up the development of antiviral agents and shed light on the preparation for potential coronavirus emergency in the future.Database url: http://www.zhounan.org/h2v

Proteome analysis of virulent Aeromonas hydrophila reveals the upregulation of iron acquisition systems in the presence of a xenosiderophore

2020 ◽  
Vol 367 (20) ◽  
Author(s):  
Miles D Lange ◽  
Jason Abernathy ◽  
Craig A Shoemaker ◽  
Dunhua Zhang ◽  
Augustus Kirby ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Ictalurus Punctatus ◽  
Aeromonas Hydrophila ◽  
Iron Acquisition ◽  
Chelating Agent ◽  
Proteome Analysis ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Protein Protein Interactions ◽  
Virulent Aeromonas Hydrophila

ABSTRACT The Gram-negative bacterium, Aeromonas hydrophila, has been responsible for extensive losses in the catfish industry for over a decade. Due to this impact, there are ongoing efforts to understand the basic mechanisms that contribute to virulent A. hydrophila (vAh) outbreaks. Recent challenge models demonstrated that vAh cultured in the presence of the iron chelating agent deferoxamine mesylate (DFO) were more virulent to channel catfish (Ictalurus punctatus). Interestingly, differential gene expression of select iron acquisition genes was unremarkable between DFO and non-DFO cultures, posing the question: why the increased virulence? The current work sought to evaluate growth characteristics and protein expression of vAh after the addition of DFO. A comparative proteome analysis revealed differentially expressed proteins among tryptic soy broth (TSB) and TSB + DFO treatments. Upregulated proteins identified among the TSB + DFO treatment were enriched for gene ontology groups including iron ion transport, siderophore transport and siderophore uptake transport, all iron acquisition pathways. Protein-protein interactions were also evaluated among the differentially expressed proteins and predicted that many of the upregulated iron acquisition proteins likely form functional physiological networks. The proteome analysis of the vAh reveals valuable information about the basic biological processes likely leading to increased virulence during iron restriction in this organism.

Protein–protein interactions of HPV–Chlamydia trachomatis–human and their potential in cervical cancer

2020 ◽  
Vol 15 (7) ◽  
pp. 509-520
Author(s):  
Abdul Arif Khan ◽  
Abdulwahab A Abuderman ◽  
Mohd Tashfeen Ashraf ◽  
Zakir Khan
Keyword(s):  
Cervical Cancer ◽  
Chlamydia Trachomatis ◽  
Protein Interactions ◽  
Cancer Development ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Pathogen Protein ◽  
Associated Proteins ◽  
Human Proteins ◽  
Cervical Cancer Development

Aim: HPV is an important cause of cervical cancer, but Chlamydia trachomatis (CT) is suspiciously involved in this disease ranging from direct to its involvement as a cofactor with HPV. We performed this study to understand the interaction of HPV and C. trachomatis with humans and its contribution to cervical cancer. Materials & methods: Host–pathogen and pathogen–pathogen protein–protein interaction maps of HPV/CT/human were prepared and compared to analyze interactions during single/coinfection of C. trachomatis and HPV. The interacting human proteins were detected by their involvement in cervical cancer. Results: C. trachomatis may interact with several cancer associated proteins while HPV and C. trachomatis largely interact with different human proteins, suggesting different pathogenesis. Conclusion: C. trachomatis coinfection with HPV may modulate cervical cancer development.

scholarly journals Potential Anticancer Mechanisms of a Novel EGFR/DNA-Targeting Combi-Molecule (JDF12) against DU145 Prostate Cancer Cells: An iTRAQ-Based Proteomic Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-12
Author(s):  
Haofeng Zheng ◽  
Guancan Liang ◽  
Yanxiong Chen ◽  
Sijie Lin ◽  
Wei Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Application ◽  
Protein Interactions ◽  
Annexin V ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Protein Protein Interactions ◽  
Absolute Quantitation ◽  
Anticancer Efficacy ◽  
Isobaric Tags

The development of multitargeting drugs is an emerging trend in cancer research. To promote further development and clinical application of multitargeting drugs, this research was performed. MTT assay and flow cytometry of Annexin V/propidium iodide staining were used to confirm the proapoptotic efficacy of a novel combi-targeting molecule, JDF12, against DU145 prostate cancer (PCa) cells. Differentially expressed proteins between control and JDF12-treated cultures were revealed by isobaric tags for relative and absolute quantitation (iTRAQ), and part of them was confirmed by quantitative PCR. Differentially expressed proteins were further analyzed for function, pathway association, and protein−protein interactions using GO, KEGG, and STRING databases. A total of 119 differentially expressed proteins, 70 upregulated and 49 downregulated, were implicated in the anticancer effects of JDF12. Many of these proteins are involved in biosynthesis, response to stress, energy metabolism, and signal transduction. This study provides important information for understanding the anti-PCa mechanisms of JDF12, and well-designed combi-targeting drugs may possess stronger anticancer efficacy than single-targeting drugs and are thus promising candidates for clinical application.

scholarly journals Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades

2021 ◽  
Vol 22 (12) ◽  
pp. 6373
Author(s):  
Ahmad Jalloh ◽  
Antwoine Flowers ◽  
Charles Hudson ◽  
Dale Chaput ◽  
Jennifer Guergues ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Control Diet ◽  
Bioinformatic Analysis ◽  
Diet Group ◽  
Differentially Expressed ◽  
Signaling Cascades ◽  
Complex Nature ◽  
Differentially Expressed Proteins ◽  
Ms Analysis ◽  
Age Related

Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.

Leucine periodicity of U2 small nuclear ribonucleoprotein particle (snRNP) A' protein is implicated in snRNP assembly via protein-protein interactions

1991 ◽  
Vol 11 (3) ◽  
pp. 1578-1589
Author(s):  
L D Fresco ◽  
D S Harper ◽  
J D Keene
Keyword(s):  
Protein Interactions ◽  
Leucine Zipper ◽  
Tandem Repeats ◽  
Mutational Analysis ◽  
Particle Density ◽  
Protein Protein Interactions ◽  
Small Nuclear Ribonucleoprotein ◽  
Cell Extracts ◽  
Associated Proteins ◽  
Nuclear Ribonucleoprotein

Recombinant A' protein could be reconstituted into U2 small nuclear ribonucleoprotein particles (snRNPs) upon addition to HeLa cell extracts as determined by coimmunoprecipitation and particle density; however, direct binding to U2 RNA could not be demonstrated except in the presence of the U2 snRNP B" protein. Mutational analysis indicated that a central core region of A' was required for particle reconstitution. This region consists of five tandem repeats of approximately 24 amino acids each that exhibit a periodicity of leucine and asparagine residues that is distinct from the leucine zipper. Similar leucine-rich (Leu-Leu motif) repeats are characteristic of a diverse array of soluble and membrane-associated proteins from yeasts to humans but have not been reported previously to reside in nuclear proteins. Several of these proteins, including Toll, chaoptin, RNase/angiogenin inhibitors, lutropin-choriogonadotropin receptor, carboxypeptidase N, adenylyl cyclase, CD14, and human immunodeficiency virus type 1 Rev, may be involved in protein-protein interactions. Our findings suggest that in cell extracts the Leu-Leu motif of A' is required for reconstitution with U2 snRNPs and perhaps with other components involved in splicing through protein-protein interactions.

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 Group I Metabotropic Glutamate Receptors and Interacting Partners: An Update

2022 ◽  
Vol 23 (2) ◽  
pp. 840
Author(s):  
Li-Min Mao ◽  
Alaya Bodepudi ◽  
Xiang-Ping Chu ◽  
John Q. Wang
Keyword(s):  
Synaptic Plasticity ◽  
Protein Interactions ◽  
Metabotropic Glutamate Receptors ◽  
Adaptor Proteins ◽  
Mammalian Brain ◽  
Amino Acid Residues ◽  
Protein Protein Interactions ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Associated Proteins

Group I metabotropic glutamate (mGlu) receptors (mGlu1/5 subtypes) are G protein-coupled receptors and are broadly expressed in the mammalian brain. These receptors play key roles in the modulation of normal glutamatergic transmission and synaptic plasticity, and abnormal mGlu1/5 signaling is linked to the pathogenesis and symptomatology of various mental and neurological disorders. Group I mGlu receptors are noticeably regulated via a mechanism involving dynamic protein–protein interactions. Several synaptic protein kinases were recently found to directly bind to the intracellular domains of mGlu1/5 receptors and phosphorylate the receptors at distinct amino acid residues. A variety of scaffolding and adaptor proteins also interact with mGlu1/5. Constitutive or activity-dependent interactions between mGlu1/5 and their interacting partners modulate trafficking, anchoring, and expression of the receptors. The mGlu1/5-associated proteins also finetune the efficacy of mGlu1/5 postreceptor signaling and mGlu1/5-mediated synaptic plasticity. This review analyzes the data from recent studies and provides an update on the biochemical and physiological properties of a set of proteins or molecules that interact with and thus regulate mGlu1/5 receptors.

scholarly journals An Integrative Computational Approach for the Prediction of Human-Plasmodium Protein-Protein Interactions

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Kais Ghedira ◽  
Yosr Hamdi ◽  
Abir El Béji ◽  
Houcemeddine Othman
Keyword(s):  
Protein Interactions ◽  
Computational Approach ◽  
Protein Protein Interactions ◽  
Human Red Blood Cells ◽  
Pharmacological Targets ◽  
Host Pathogen ◽  
Human Proteins ◽  
Life Threatening ◽  
Similarity Method ◽  
Human Plasmodium

Host-pathogen molecular cross-talks are critical in determining the pathophysiology of a specific infection. Most of these cross-talks are mediated via protein-protein interactions between the host and the pathogen (HP-PPI). Thus, it is essential to know how some pathogens interact with their hosts to understand the mechanism of infections. Malaria is a life-threatening disease caused by an obligate intracellular parasite belonging to the Plasmodium genus, of which P. falciparum is the most prevalent. Several previous studies predicted human-plasmodium protein-protein interactions using computational methods have demonstrated their utility, accuracy, and efficiency to identify the interacting partners and therefore complementing experimental efforts to characterize host-pathogen interaction networks. To predict potential putative HP-PPIs, we use an integrative computational approach based on the combination of multiple OMICS-based methods including human red blood cells (RBC) and Plasmodium falciparum 3D7 strain expressed proteins, domain-domain based PPI, similarity of gene ontology terms, structure similarity method homology identification, and machine learning prediction. Our results reported a set of 716 protein interactions involving 302 human proteins and 130 Plasmodium proteins. This work provides a list of potential human-Plasmodium interacting proteins. These findings will contribute to better understand the mechanisms underlying the molecular determinism of malaria disease and potentially to identify candidate pharmacological targets.

A silencer is required for maintenance of transcriptional repression throughout Drosophila development

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4343-4350 ◽  
Author(s):  
A. Busturia ◽  
C.D. Wightman ◽  
S. Sakonju
Keyword(s):  
Protein Interactions ◽  
Transcriptional Repression ◽  
Transcriptional Silencing ◽  
Active Role ◽  
Polycomb Group ◽  
Homeotic Genes ◽  
Protein Protein Interactions ◽  
Drosophila Development ◽  
Larval Stages ◽  
Associated Proteins

Transcriptional silencing by the Polycomb Group of genes maintains the position-specific repression of homeotic genes throughout Drosophila development. The Polycomb Group of genes characterized to date encode chromatin-associated proteins that have been suggested to form heterochromatin-like structures. By studying the expression of reporter genes, we have identified a 725 bp fragment, called MCP725, in the homeotic gene Abdominal-B, that accurately maintains position-specific silencing during proliferation of imaginal cells. Silencing by MCP725 requires the Polycomb and the Polycomblike genes, indicating that it contains a Polycomb response element To investigate the mechanisms of transcriptional silencing by MCP725, we have studied its temporal requirements by removing MCP725 from the transgene at various times during development. We have discovered that excision of MCP725 during larval stages leads to loss of silencing. Our findings indicate that the silencer is required for the maintenance of the repressed state throughout cell proliferation. They also suggest that propagation of the silenced state does not occur merely by templating of a heterochromatin structure by virtue of protein-protein interactions. Rather, they suggest that silencers play an active role in the maintenance of the position-specific repression throughout development.

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