scholarly journals Lipid signaling to membrane proteins: From second messengers to membrane domains and adapter-free endocytosis

2018 ◽  
Vol 150 (2) ◽  
pp. 211-224 ◽  
Author(s):  
Donald W. Hilgemann ◽  
Gucan Dai ◽  
Anthony Collins ◽  
Vincenzo Larricia ◽  
Simona Magi ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Second Messengers ◽  
Surface Membrane ◽  
Short Review ◽  
Lipid Signaling ◽  
Membrane Domains ◽  
Protein Protein Interactions ◽  
Protein Membrane ◽  
Bona Fide ◽  
And Control

Lipids influence powerfully the function of ion channels and transporters in two well-documented ways. A few lipids act as bona fide second messengers by binding to specific sites that control channel and transporter gating. Other lipids act nonspecifically by modifying the physical environment of channels and transporters, in particular the protein–membrane interface. In this short review, we first consider lipid signaling from this traditional viewpoint, highlighting innumerable Journal of General Physiology publications that have contributed to our present understanding. We then switch to our own emerging view that much important lipid signaling occurs via the formation of membrane domains that influence the function of channels and transporters within them, promote selected protein–protein interactions, and control the turnover of surface membrane.

scholarly journals PIPINO: A Software Package to Facilitate the Identification of Protein-Protein Interactions from Affinity Purification Mass Spectrometry Data

2016 ◽  
Vol 2016 ◽  
pp. 1-13
Author(s):  
Stefan Kalkhof ◽  
Stefan Schildbach ◽  
Conny Blumert ◽  
Friedemann Horn ◽  
Martin von Bergen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Interactions ◽  
Isotope Labeling ◽  
Affinity Purification ◽  
Interaction Network ◽  
Mass Spectrometry Data ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Binding Behavior ◽  
Bona Fide

The functionality of most proteins is regulated by protein-protein interactions. Hence, the comprehensive characterization of the interactome is the next milestone on the path to understand the biochemistry of the cell. A powerful method to detect protein-protein interactions is a combination of coimmunoprecipitation or affinity purification with quantitative mass spectrometry. Nevertheless, both methods tend to precipitate a high number of background proteins due to nonspecific interactions. To address this challenge the software Protein-Protein-Interaction-Optimizer (PIPINO) was developed to perform an automated data analysis, to facilitate the selection of bona fide binding partners, and to compare the dynamic of interaction networks. In this study we investigated the STAT1 interaction network and its activation dependent dynamics. Stable isotope labeling by amino acids in cell culture (SILAC) was applied to analyze the STAT1 interactome after streptavidin pull-down of biotagged STAT1 from human embryonic kidney 293T cells with and without activation. Starting from more than 2,000 captured proteins 30 potential STAT1 interaction partners were extracted. Interestingly, more than 50% of these were already reported or predicted to bind STAT1. Furthermore, 16 proteins were found to affect the binding behavior depending on STAT1 phosphorylation such as STAT3 or the importin subunits alpha 1 and alpha 6.

Tyrosine-O-sulfation is a widespread affinity enhancer among thrombin interactors

2022 ◽  
Author(s):  
Jorge Ripoll-Rozada ◽  
Joshua W. C. Maxwell ◽  
Richard J. Payne ◽  
Pedro José Barbosa Pereira
Keyword(s):  
Protein Interactions ◽  
Secretory Pathway ◽  
Serine Proteinase ◽  
Blood Feeding ◽  
Thrombin Inhibitor ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Human Fibrinogen ◽  
Clotting Cascade ◽  
Bona Fide

Tyrosine-O-sulfation is a common post-translational modification (PTM) of proteins following the cellular secretory pathway. First described in human fibrinogen, tyrosine-O-sulfation has long been associated with the modulation of protein–protein interactions in several physiological processes. A number of relevant interactions for hemostasis are largely dictated by this PTM, many of which involving the serine proteinase thrombin (FIIa), a central player in the blood-clotting cascade. Tyrosine sulfation is not limited to endogenous FIIa ligands and has also been found in hirudin, a well-known and potent thrombin inhibitor from the medicinal leech, Hirudo medicinalis. The discovery of hirudin led to successful clinical application of analogs of leech-inspired molecules, but also unveiled several other natural thrombin-directed anticoagulant molecules, many of which undergo tyrosine-O-sulfation. The presence of this PTM has been shown to enhance the anticoagulant properties of these peptides from a range of blood-feeding organisms, including ticks, mosquitos and flies. Interestingly, some of these molecules display mechanisms of action that mimic those of thrombin's bona fide substrates.

scholarly journals Photoswitchable peptide-based ‘on-off’ biosensor for electrochemical detection and control of protein-protein interactions

2018 ◽  
Vol 118 ◽  
pp. 188-194 ◽  
Author(s):  
John R. Horsley ◽  
Jingxian Yu ◽  
Kate L. Wegener ◽  
Christian Hoppmann ◽  
Karola Rück-Braun ◽  
...  
Keyword(s):  
Electrochemical Detection ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
And Control

Effect of Intestinal Flora Clearance on Liver Proteomics in Mice

2019 ◽  
Vol 16 (3) ◽  
pp. 199-209
Author(s):  
Zhenghu Jia ◽  
Hui Liu ◽  
Mei Song ◽  
Chengmao Yang ◽  
Yapu Zhao ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Concanavalin A ◽  
Intestinal Flora ◽  
Label Free ◽  
Protein Protein Interactions ◽  
Rt Pcr ◽  
Proteome Level ◽  
And Control ◽  
The Relationship ◽  
Free Quantification

Background: Intestinal flora dynamically affects the host&#039;s systemic immune system. Liver is one of the organs that may be affected by intestinal microbiota. </P><P> Materials and Methods: In this study, we aimed to identify proteome level differences between liver tissue from mice cleared intestinal flora and control using tandem mass spectrometry (LC-MS/MS) and label free quantification. Additionally, protein-protein interactions were mapped by STRING, and also, the enrichment of inflammation-related signaling pathways and biological processes was identified using GO and IPA network system. RT-PCR and Western blot were used for validation of the proteomics findings. Results: Our study demonstrated that mice with cleared intestinal flora exhibited decreased sensitivity to Concanavalin A induced acute hepatitis. 324 Proteins in liver were differently expressed after intestinal flora clearance for one week while 210 proteins were differently expressed after intestinal flora clearance for two weeks. Furthermore, five of the identified proteins were validated by western blotting and further investigated by semi-quantitative RT-PCR. Conclusion: Our results showed that intestinal flora clearance in mice could reduce sensitivity to Concanavalin A induced liver injury and influence the expression of proteins in liver, which provides a clue for studying the relationship between gut bacteria and Concanavalin A induced hepatitis.

scholarly journals Correction: Lipid signaling to membrane proteins: From second messengers to membrane domains and adapter-free endocytosis

2018 ◽  
Vol 150 (2) ◽  
pp. 367-367 ◽  
Author(s):  
Donald W. Hilgemann ◽  
Gucan Dai ◽  
Anthony Collins ◽  
Vincenzo Lariccia ◽  
Simona Magi ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Second Messengers ◽  
Lipid Signaling ◽  
Membrane Domains

scholarly journals The interactome: Predicting the protein-protein interactions in cells

2009 ◽  
Vol 14 (1) ◽  
pp. 1-22 ◽  
Author(s):  
Dariusz Plewczyński ◽  
Krzysztof Ginalski
Keyword(s):  
Protein Interactions ◽  
Three Dimensional ◽  
Short Review ◽  
Amino Acid Sequences ◽  
Protein Protein Interactions ◽  
Structure Information ◽  
Cellular Processes ◽  
Molecular Machinery ◽  
Genome Scale ◽  
In Cells

AbstractThe term Interactome describes the set of all molecular interactions in cells, especially in the context of protein-protein interactions. These interactions are crucial for most cellular processes, so the full representation of the interaction repertoire is needed to understand the cell molecular machinery at the system biology level. In this short review, we compare various methods for predicting protein-protein interactions using sequence and structure information. The ultimate goal of those approaches is to present the complete methodology for the automatic selection of interaction partners using their amino acid sequences and/or three dimensional structures, if known. Apart from a description of each method, details of the software or web interface needed for high throughput prediction on the whole genome scale are also provided. The proposed validation of the theoretical methods using experimental data would be a better assessment of their accuracy.

scholarly journals Interactome Data and Databases: Different Types of Protein Interaction

2004 ◽  
Vol 5 (2) ◽  
pp. 173-178 ◽  
Author(s):  
Javier De Las Rivas ◽  
Alberto de Luis
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Interaction Network ◽  
Short Review ◽  
Experimental Methods ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Genome Wide ◽  
Bioinformatic Tool ◽  
Different Types

In recent years, the biomolecular sciences have been driven forward by overwhelming advances in new biotechnological high-throughput experimental methods and bioinformatic genome-wide computational methods. Such breakthroughs are producing huge amounts of new data that need to be carefully analysed to obtain correct and useful scientific knowledge. One of the fields where this advance has become more intense is the study of the network of ‘protein–protein interactions’, i.e. the ‘interactome’. In this short review we comment on the main data and databases produced in this field in last 5 years. We also present a rationalized scheme of biological definitions that will be useful for a better understanding and interpretation of ‘what a protein–protein interaction is’ and ‘which types of protein–protein interactions are found in a living cell’. Finally, we comment on some assignments of interactome data to defined types of protein interaction and we present a new bioinformatic tool called APIN (Agile Protein Interaction Network browser), which is in development and will be applied to browsing protein interaction databases.

scholarly journals The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator of C. elegans development

2016 ◽  
Author(s):  
Markéta Kostrouchová ◽  
David Kostrouch ◽  
Ahmed A Chughtai ◽  
Filip Kaššák ◽  
Jan P. Novotný ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Protein Interactions ◽  
Structural Proteins ◽  
Mediator Complex ◽  
Cytoplasmic Localization ◽  
Protein Protein Interactions ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Nuclear Events ◽  
Bona Fide

The evolutionarily conserved Mediator complex is a critical player in regulating transcription. Comprised of approximately two dozen proteins, Mediator integrates diverse regulatory signals through direct protein-protein interactions that, in turn, modulate the influence of Mediator on RNA Polymerase II activity. One Mediator subunit, MED28, is known to interact with cytoplasmic structural proteins, providing a potential direct link between cytoplasmic dynamics and the control of gene transcription. Although identified in many animals and plants, MED28 is not present in yeast; no bona fide MED28 has been described previously in C. elegans. Here, we identify bioinformatically F28F8.5, an uncharacterized predicted protein, as the nematode homologue of MED28. As in other metazoa, F28F8.5 has dual nuclear and cytoplasmic localization and plays critical roles in the regulation of development. F28F8.5 is a vital gene and its null mutants have severely malformed gonads and do not reproduce. Our results indicate that F28F8.5 is a homologue of MED28 and suggest that the potential to link cytoplasmic and nuclear events is conserved between MED28 vertebrate and nematode homologues.

How Cancer Cells Resist Chemotherapy: Design and Development of Drugs Targeting Protein-Protein Interactions

2019 ◽  
Vol 19 (6) ◽  
pp. 394-412 ◽  
Author(s):  
Vadim V. Tarasov ◽  
Vladimir N. Chubarev ◽  
Ghulam Md Ashraf ◽  
Samira A. Dostdar ◽  
Alexander V. Sokolov ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Clinical Outcome ◽  
Cancer Cells ◽  
Protein Interactions ◽  
Resistance Mechanisms ◽  
Protein Protein Interactions ◽  
Treatment Regimens ◽  
Pubmed Search ◽  
Bona Fide ◽  
Improve Clinical Outcome

Background:Resistance toward chemotherapeutics is one of the main obstacles on the way to effective cancer treatment. Personalization of chemotherapy could improve clinical outcome. However, despite preclinical significance, most of the potential markers have failed to reach clinical practice partially due to the inability of numerous studies to estimate the marker’s impact on resistance properly.Objective:The analysis of drug resistance mechanisms to chemotherapy in cancer cells, and the proposal of study design to identify bona fide markers.Methods:A review of relevant papers in the field. A PubMed search with relevant keywords was used to gather the data. An example of a search request: drug resistance AND cancer AND paclitaxel.Results:We have described a number of drug resistance mechanisms to various chemotherapeutics, as well as markers to underlie the phenomenon. We also proposed a model of a rational-designed study, which could be useful in determining the most promising potential biomarkers.Conclusion:Taking into account the most reasonable biomarkers should dramatically improve clinical outcome by choosing the suitable treatment regimens. However, determining the leading biomarkers, as well as validating of the model, is a work for further investigations.

scholarly journals The Src Family Kinases, Fgr, Fyn, Lck, and Lyn, Colocalize With Coated Membranes in Platelets

Blood ◽  
1997 ◽  
Vol 89 (7) ◽  
pp. 2384-2393 ◽  
Author(s):  
Paula E. Stenberg ◽  
Tamara I. Pestina ◽  
Rosemary J. Barrie ◽  
Carl W. Jackson
Keyword(s):  
Protein Interactions ◽  
Tyrosine Kinases ◽  
Intracellular Signaling ◽  
Cell Types ◽  
Coated Vesicle ◽  
Specific Cell ◽  
Membrane Domains ◽  
Protein Protein Interactions ◽  
Coated Pits ◽  
Coated Membranes

Abstract Nonreceptor protein tyrosine kinases phosphorylate proteins, thereby activating many intracellular signaling pathways and mediating protein-protein interactions. Protein phosphorylation is regulated in large part by the subcellular localization of these kinases and their respective substrates. Src is the most studied of these kinases, although other members of the Src family have been shown to be important in the differentiation of specific cell types. Src and Src family members are reported to be membrane-associated, but detergent-extraction studies have demonstrated a major difference in the solubility of Src compared with other members of the Src family (Fgr, Fyn, Lck, Lyn, and Yes), suggesting that their subcellular distributions may be different. By immunoelectron microscopy, we demonstrate that, unlike Src, the Src-related kinases are associated with electron-dense cytoplasmic domains and plasma membrane domains that correspond in size and frequency to endocytotic vesicles and coated pits. Clusters of labeling for these kinases also were seen adjacent to granule membranes. These kinases colocalize with the coated vesicle protein, clathrin, confirming their association with this class of endocytotic vesicle. We hypothesize that this vesicular association of Src-related kinases indicates a role for them in the endocytotic vesicle–mediated uptake and trafficking of plasma proteins into platelet granules.

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