scholarly journals LMPID: A manually curated database of linear motifs mediating protein–protein interactions

Database ◽  
2015 ◽  
Vol 2015 ◽  
Author(s):  
Debasree Sarkar ◽  
Tanmoy Jana ◽  
Sudipto Saha
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Linear Motifs

scholarly journals Short Linear Motifs Characterizing Snake Venom and Mammalian Phospholipases A2

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 290
Author(s):  
Caterina Peggion ◽  
Fiorella Tonello
Keyword(s):  
Snake Venom ◽  
Protein Interactions ◽  
Biological Properties ◽  
Protein Protein Interactions ◽  
Sequence Alignments ◽  
Toxic Activity ◽  
Short Linear Motifs ◽  
Phospholipases A2 ◽  
Group I ◽  
Linear Motifs

Snake venom phospholipases A2 (PLA2s) have sequences and structures very similar to those of mammalian group I and II secretory PLA2s, but they possess many toxic properties, ranging from the inhibition of coagulation to the blockage of nerve transmission, and the induction of muscle necrosis. The biological properties of these proteins are not only due to their enzymatic activity, but also to protein–protein interactions which are still unidentified. Here, we compare sequence alignments of snake venom and mammalian PLA2s, grouped according to their structure and biological activity, looking for differences that can justify their different behavior. This bioinformatics analysis has evidenced three distinct regions, two central and one C-terminal, having amino acid compositions that distinguish the different categories of PLA2s. In these regions, we identified short linear motifs (SLiMs), peptide modules involved in protein–protein interactions, conserved in mammalian and not in snake venom PLA2s, or vice versa. The different content in the SLiMs of snake venom with respect to mammalian PLA2s may result in the formation of protein membrane complexes having a toxic activity, or in the formation of complexes whose activity cannot be blocked due to the lack of switches in the toxic PLA2s, as the motif recognized by the prolyl isomerase Pin1.

scholarly journals Peptide-based Interaction Proteomics

2020 ◽  
Vol 19 (7) ◽  
pp. 1070-1075 ◽  
Author(s):  
Katrina Meyer ◽  
Matthias Selbach
Keyword(s):  
Protein Interactions ◽  
Synthetic Peptides ◽  
Protein Protein Interactions ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Interaction Partners ◽  
Linear Motifs ◽  
Cellulose Membranes ◽  
Interaction Proteomics ◽  
Proteins Interactions

Protein-protein interactions are often mediated by short linear motifs (SLiMs) that are located in intrinsically disordered regions (IDRs) of proteins. Interactions mediated by SLiMs are notoriously difficult to study, and many functionally relevant interactions likely remain to be uncovered. Recently, pull-downs with synthetic peptides in combination with quantitative mass spectrometry emerged as a powerful screening approach to study protein-protein interactions mediated by SLiMs. Specifically, arrays of synthetic peptides immobilized on cellulose membranes provide a scalable means to identify the interaction partners of many peptides in parallel. In this minireview we briefly highlight the relevance of SLiMs for protein-protein interactions, outline existing screening technologies, discuss unique advantages of peptide-based interaction screens and provide practical suggestions for setting up such peptide-based screens.

scholarly journals Orchestrating serine/threonine phosphorylation and elucidating downstream effects by short linear motifs

2022 ◽  
Vol 479 (1) ◽  
pp. 1-22
Author(s):  
Johanna Kliche ◽  
Ylva Ivarsson
Keyword(s):  
Complex Formation ◽  
Protein Interactions ◽  
Binding Sites ◽  
Protein Protein Interactions ◽  
Post Translational Modifications ◽  
Short Linear Motifs ◽  
Protein Complex Formation ◽  
Downstream Effects ◽  
Linear Motifs ◽  
Threonine Kinases

Cellular function is based on protein–protein interactions. A large proportion of these interactions involves the binding of short linear motifs (SLiMs) by folded globular domains. These interactions are regulated by post-translational modifications, such as phosphorylation, that create and break motif binding sites or tune the affinity of the interactions. In addition, motif-based interactions are involved in targeting serine/threonine kinases and phosphatases to their substrate and contribute to the specificity of the enzymatic actions regulating which sites are phosphorylated. Here, we review how SLiM-based interactions assist in determining the specificity of serine/threonine kinases and phosphatases, and how phosphorylation, in turn, affects motif-based interactions. We provide examples of SLiM-based interactions that are turned on/off, or are tuned by serine/threonine phosphorylation and exemplify how this affects SLiM-based protein complex formation.

scholarly journals Systematic discovery of Short Linear Motifs decodes calcineurin phosphatase signaling

2019 ◽  
Author(s):  
Callie P. Wigington ◽  
Jagoree Roy ◽  
Nikhil P. Damle ◽  
Vikash K. Yadav ◽  
Cecilia Blikstad ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Nuclear Pore ◽  
Binding Affinities ◽  
Protein Protein Interactions ◽  
Short Linear Motifs ◽  
Binding Peptides ◽  
Linear Motifs ◽  
Calcineurin Phosphatase

SummaryShort linear motifs (SLiMs) drive dynamic protein-protein interactions essential for signaling, but sequence degeneracy and low binding affinities make them difficult to identify. We harnessed unbiased systematic approaches for SLiM discovery to elucidate the regulatory network of calcineurin (CN)/PP2B, the Ca2+-activated phosphatase that recognizes LxVP and PxIxIT motifs. In vitro proteome-wide detection of CN-binding peptides, in vivo SLiM-dependent proximity labeling, and in silico modeling of motif determinants uncovered unanticipated CN interactors, including NOTCH1, which we establish as a CN substrate. Unexpectedly, CN shows SLiM-dependent proximity to centrosomal and nuclear pore complex (NPC) proteins – structures where Ca2+ signaling is largely uncharacterized. CN dephosphorylates human and yeast NPC proteins and promotes accumulation of a nuclear transport reporter, suggesting conserved NPC regulation by CN. The CN network assembled here provides a resource to investigate Ca2+ and CN signaling and demonstrates synergy between experimental and computational methods, establishing a blueprint for examining SLiM-based networks.

scholarly journals Peptide array–based interactomics

2021 ◽  
Author(s):  
Daniel Perez Hernandez ◽  
Gunnar Dittmar
Keyword(s):  
Amino Acid ◽  
Protein Interactions ◽  
Large Scale ◽  
New Technologies ◽  
Membrane Surface ◽  
Protein Protein Interactions ◽  
Post Translational Modifications ◽  
Short Linear Motifs ◽  
Binding Partners ◽  
Linear Motifs

AbstractThe analysis of protein-protein interactions (PPIs) is essential for the understanding of cellular signaling. Besides probing PPIs with immunoprecipitation-based techniques, peptide pull-downs are an alternative tool specifically useful to study interactome changes induced by post-translational modifications. Peptides for pull-downs can be chemically synthesized and thus offer the possibility to include amino acid exchanges and post-translational modifications (PTMs) in the pull-down reaction. The combination of peptide pull-down and analysis of the binding partners with mass spectrometry offers the direct measurement of interactome changes induced by PTMs or by amino acid exchanges in the interaction site. The possibility of large-scale peptide synthesis on a membrane surface opened the possibility to systematically analyze interactome changes for mutations of many proteins at the same time. Short linear motifs (SLiMs) are amino acid patterns that can mediate protein binding. A significant number of SLiMs are located in regions of proteins, which are lacking a secondary structure, making the interaction motifs readily available for binding reactions. Peptides are particularly well suited to study protein interactions, which are based on SLiM-mediated binding. New technologies using arrayed peptides for interaction studies are able to identify SLIM-based interaction and identify the interaction motifs. Graphical abstract

scholarly journals SLiMScape 3.x: a Cytoscape 3 app for discovery of Short Linear Motifs in protein interaction networks

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 477 ◽  
Author(s):  
Emily Olorin ◽  
Kevin T. O'Brien ◽  
Nicolas Palopoli ◽  
Åsa Pérez-Bercoff ◽  
Denis C. Shields ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Evolutionary Dynamics ◽  
De Novo ◽  
Molecular Mimicry ◽  
Interaction Networks ◽  
Protein Protein Interactions ◽  
Homologous Proteins ◽  
Short Linear Motifs ◽  
Sequence Patterns ◽  
Linear Motifs

Short linear motifs (SLiMs) are small protein sequence patterns that mediate a large number of critical protein-protein interactions, involved in processes such as complex formation, signal transduction, localisation and stabilisation. SLiMs show rapid evolutionary dynamics and are frequently the targets of molecular mimicry by pathogens. Identifying enriched sequence patterns due to convergent evolution in non-homologous proteins has proven to be a successful strategy for computational SLiM prediction. Tools of the SLiMSuite package use this strategy, using a statistical model to identify SLiM enrichment based on the evolutionary relationships, amino acid composition and predicted disorder of the input proteins. The quality of input data is critical for successful SLiM prediction. Cytoscape provides a user-friendly, interactive environment to explore interaction networks and select proteins based on common features, such as shared interaction partners. SLiMScape embeds tools of the SLiMSuite package for de novo SLiM discovery (SLiMFinder and QSLiMFinder) and identifying occurrences/enrichment of known SLiMs (SLiMProb) within this interactive framework. SLiMScape makes it easier to (1) generate high quality hypothesis-driven datasets for these tools, and (2) visualise predicted SLiM occurrences within the context of the network. To generate new predictions, users can select nodes from a protein network or provide a set of Uniprot identifiers. SLiMProb also requires additional query motif input. Jobs are then run remotely on the SLiMSuite server (http://rest.slimsuite.unsw.edu.au) for subsequent retrieval and visualisation. SLiMScape can also be used to retrieve and visualise results from jobs run directly on the server. SLiMScape and SLiMSuite are open source and freely available via GitHub under GNU licenses.

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