scholarly journals Master of all things phosphorylated

2004 ◽  
Vol 379 (1) ◽  
pp. e1-e2 ◽  
Author(s):  
Michael B. YAFFE
Keyword(s):  
Affinity Chromatography ◽  
Protein Interactions ◽  
Specific Protein ◽  
Interacting Proteins ◽  
Protein Protein Interactions ◽  
Cellular Regulation ◽  
Cellular Targets ◽  
Biochemical Journal ◽  
Wide Range ◽  
Future Work

Serine/threonine phosphorylation plays a central role in cellular regulation, either by altering a protein's activity directly or by inducing specific protein–protein interactions, which, in turn, affect localization, binding specificity or activity. One group of molecules that bind to phosphoserine/phosphothreonine-containing sequences are the 14-3-3 proteins, which regulate a wide range of cellular targets. A new analysis of the 14-3-3 phosphoproteome using affinity chromatography has revealed many previously unknown 14-3-3 ligands whose binding to 14-3-3 proteins is phosphorylation-dependent. This study by the Mackintosh group in this issue of the Biochemical Journal paves the way for future work on these important 14-3-3-interacting proteins.

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.

Plant 14-3-3 protein families: evidence for isoform-specific functions?

2002 ◽  
Vol 30 (4) ◽  
pp. 373-378 ◽  
Author(s):  
M. R. Roberts ◽  
G. L. de Bruxelles
Keyword(s):  
Protein Interactions ◽  
Expression Patterns ◽  
Specific Protein ◽  
Biochemical Properties ◽  
Protein Protein Interactions ◽  
Target Proteins ◽  
Wide Range ◽  
Isoform Specificity ◽  
Higher Eukaryotes ◽  
Target Binding

14-3-3 proteins regulate a wide range of target proteins via direct protein-protein interactions. The target-binding domain in 14-3-3 proteins is highly conserved, suggesting similar biochemical properties for all 14-3-3s. However, higher eukaryotes possess multiple 14-3-3 genes, and these genes exhibit diverse patterns of gene expression within any one organism. This tends to suggest specific functions for particular genes. Some biochemical data suggest 14-3-3 isoform-specific protein-protein interactions, whereas other studies conclude that apparent isoform-specificity is the result of differences in expression patterns rather than in the biochemical properties of 14-3-3 isoforms. Here we discuss evidence that demonstrates that the expression levels of 14-3-3 proteins in cells are important for regulating the activity of their target proteins, and further that the elimination of individual 14-3-3 isoforms can result in detectable phenotypes. We also examine evidence that 14-3-3 isoform specificity can in some cases reflect differing biochemical properties as well as differential transcriptional regulation.

scholarly journals That zincing feeling: the effects of EDTA on the behaviour of zinc-binding transcriptional regulators

2004 ◽  
Vol 381 (3) ◽  
Author(s):  
Jennifer K. NYBORG ◽  
Olve B. PEERSEN
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Chelating Agent ◽  
Specific Protein ◽  
Regulatory Proteins ◽  
Zinc Binding ◽  
Creb Binding Protein ◽  
Protein Protein Interactions ◽  
Activator Proteins ◽  
Biochemical Journal

Zinc-binding proteins account for nearly half of the transcription regulatory proteins in the human genome and are the most abundant class of proteins in the human proteome. The zinc-binding transcriptional regulatory proteins utilize Zn2+ to fold structural domains that participate in intermolecular interactions. A study by Matt et al. in this issue of the Biochemical Journal has examined the transcription factor binding properties of the zinc-binding module C/H1 (cysteine/histidine-rich region 1) found in the transcriptional co-activator proteins CBP (CREB-binding protein) and p300. Their studies revealed that EDTA treatment of native C/H1 leads to irreversible denaturation and aggregation. Of particular concern is their finding that unfolded C/H1 participates in non-specific protein–protein interactions. The implications of these results are significant. EDTA is a very potent zinc-chelating agent that is used ubiquitously in protein interaction studies and in molecular biology in general. The potentially detrimental effects of EDTA on the structure and interactions of zinc-binding proteins should be taken into account in the interpretation of a sizeable number of published studies and must be considered in future experiments.

scholarly journals Ways into Understanding HIF Inhibition

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 159
Author(s):  
Tina Schönberger ◽  
Joachim Fandrey ◽  
Katrin Prost-Fingerle
Keyword(s):  
Protein Interactions ◽  
Target Genes ◽  
Protein Protein Interactions ◽  
Low Oxygen ◽  
Drug Candidates ◽  
Open Questions ◽  
Wide Range ◽  
Hif Pathway

Hypoxia is a key characteristic of tumor tissue. Cancer cells adapt to low oxygen by activating hypoxia-inducible factors (HIFs), ensuring their survival and continued growth despite this hostile environment. Therefore, the inhibition of HIFs and their target genes is a promising and emerging field of cancer research. Several drug candidates target protein–protein interactions or transcription mechanisms of the HIF pathway in order to interfere with activation of this pathway, which is deregulated in a wide range of solid and liquid cancers. Although some inhibitors are already in clinical trials, open questions remain with respect to their modes of action. New imaging technologies using luminescent and fluorescent methods or nanobodies to complement widely used approaches such as chromatin immunoprecipitation may help to answer some of these questions. In this review, we aim to summarize current inhibitor classes targeting the HIF pathway and to provide an overview of in vitro and in vivo techniques that could improve the understanding of inhibitor mechanisms. Unravelling the distinct principles regarding how inhibitors work is an indispensable step for efficient clinical applications and safety of anticancer compounds.

Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update

2018 ◽  
Vol 25 (1) ◽  
pp. 5-21 ◽  
Author(s):  
Ylenia Cau ◽  
Daniela Valensin ◽  
Mattia Mori ◽  
Sara Draghi ◽  
Maurizio Botta
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Specific Protein ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Protein Partners ◽  
High Sequence Homology ◽  
Small Molecule Modulators

14-3-3 is a class of proteins able to interact with a multitude of targets by establishing protein-protein interactions (PPIs). They are usually found in all eukaryotes with a conserved secondary structure and high sequence homology among species. 14-3-3 proteins are involved in many physiological and pathological cellular processes either by triggering or interfering with the activity of specific protein partners. In the last years, the scientific community has collected many evidences on the role played by seven human 14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate the molecular mechanisms associated to these diseases by interacting with (i) oncogenic and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate complete understanding of the physiological role of these proteins, and might offer valuable therapeutic approaches for these critical pathological states.

scholarly journals Novel Roles of SH2 and SH3 Domains in Lipid Binding

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1191
Author(s):  
Szabolcs Sipeki ◽  
Kitti Koprivanacz ◽  
Tamás Takács ◽  
Anita Kurilla ◽  
Loretta László ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Specific Protein ◽  
Lipid Binding ◽  
Sh2 Domain ◽  
Essential Property ◽  
Cellular Regulation ◽  
Sh3 Domains ◽  
Protein Partners ◽  
Interaction Domains ◽  
Central Paradigm

Signal transduction, the ability of cells to perceive information from the surroundings and alter behavior in response, is an essential property of life. Studies on tyrosine kinase action fundamentally changed our concept of cellular regulation. The induced assembly of subcellular hubs via the recognition of local protein or lipid modifications by modular protein interactions is now a central paradigm in signaling. Such molecular interactions are mediated by specific protein interaction domains. The first such domain identified was the SH2 domain, which was postulated to be a reader capable of finding and binding protein partners displaying phosphorylated tyrosine side chains. The SH3 domain was found to be involved in the formation of stable protein sub-complexes by constitutively attaching to proline-rich surfaces on its binding partners. The SH2 and SH3 domains have thus served as the prototypes for a diverse collection of interaction domains that recognize not only proteins but also lipids, nucleic acids, and small molecules. It has also been found that particular SH2 and SH3 domains themselves might also bind to and rely on lipids to modulate complex assembly. Some lipid-binding properties of SH2 and SH3 domains are reviewed here.

Identification of a C/EBP-Rel complex in avian lymphoid cells

1994 ◽  
Vol 14 (10) ◽  
pp. 6635-6646
Author(s):  
J A Diehl ◽  
M Hannink
Keyword(s):  
Gene Expression ◽  
Affinity Chromatography ◽  
Protein Interactions ◽  
Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Lymphoid Cells ◽  
Cytokine Gene Expression ◽  
Protein Protein Interactions ◽  
Dna Complex ◽  
Dna Affinity Chromatography

Protein-protein interactions between the CCAAT box enhancer-binding proteins (C/EBP) and the Rel family of transcription factors have been implicated in the regulation of cytokine gene expression. We have used sequence-specific DNA affinity chromatography to purify a complex from avian T cells that binds to a consensus C/EBP motif. Our results provide evidence that Rel-related proteins are components of the C/EBP-DNA complex as a result of protein-protein interactions with the C/EBP proteins. A polyclonal antiserum raised against the Rel homology domain of v-Rel and antisera raised against two human RelA-derived peptides specifically induced a supershift of the C/EBP-DNA complex in mobility shift assays using the affinity-purified C/EBP. In addition, several kappa B-binding proteins copurified with the avian C/EBP complex through two rounds of sequence-specific DNA affinity chromatography. The kappa B-binding proteins are distinct from the C/EBP proteins that directly contact DNA containing the C/EBP binding site. The identification of a protein complex that binds specifically to a consensus C/EBP site and contains both C/EBP and Rel family members suggests a novel mechanism for regulation of gene expression by Rel family proteins.

Elucidating Protein-protein Interactions Through Computational Approaches and Designing Small Molecule Inhibitors Against them for Various Diseases

2018 ◽  
Vol 18 (20) ◽  
pp. 1719-1736 ◽  
Author(s):  
Sharanya Sarkar ◽  
Khushboo Gulati ◽  
Manikyaprabhu Kairamkonda ◽  
Amit Mishra ◽  
Krishna Mohan Poluri
Keyword(s):  
Small Molecule ◽  
Protein Interactions ◽  
Small Molecule Inhibitors ◽  
Computational Techniques ◽  
Protein Protein Interactions ◽  
Computational Tools ◽  
Computational Approaches ◽  
Protein Protein Interaction ◽  
Wide Range ◽  
Therapeutic Measures

Background: To carry out wide range of cellular functionalities, proteins often associate with one or more proteins in a phenomenon known as Protein-Protein Interaction (PPI). Experimental and computational approaches were applied on PPIs in order to determine the interacting partners, and also to understand how an abnormality in such interactions can become the principle cause of a disease. Objective: This review aims to elucidate the case studies where PPIs involved in various human diseases have been proven or validated with computational techniques, and also to elucidate how small molecule inhibitors of PPIs have been designed computationally to act as effective therapeutic measures against certain diseases. Results: Computational techniques to predict PPIs are emerging rapidly in the modern day. They not only help in predicting new PPIs, but also generate outputs that substantiate the experimentally determined results. Moreover, computation has aided in the designing of novel inhibitor molecules disrupting the PPIs. Some of them are already being tested in the clinical trials. Conclusion: This review delineated the classification of computational tools that are essential to investigate PPIs. Furthermore, the review shed light on how indispensable computational tools have become in the field of medicine to analyze the interaction networks and to design novel inhibitors efficiently against dreadful diseases in a shorter time span.

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