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1.
Nucleic Acids Res ; 50(D1): D497-D508, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-2232151

ABSTRACT

Almost twenty years after its initial release, the Eukaryotic Linear Motif (ELM) resource remains an invaluable source of information for the study of motif-mediated protein-protein interactions. ELM provides a comprehensive, regularly updated and well-organised repository of manually curated, experimentally validated short linear motifs (SLiMs). An increasing number of SLiM-mediated interactions are discovered each year and keeping the resource up-to-date continues to be a great challenge. In the current update, 30 novel motif classes have been added and five existing classes have undergone major revisions. The update includes 411 new motif instances mostly focused on cell-cycle regulation, control of the actin cytoskeleton, membrane remodelling and vesicle trafficking pathways, liquid-liquid phase separation and integrin signalling. Many of the newly annotated motif-mediated interactions are targets of pathogenic motif mimicry by viral, bacterial or eukaryotic pathogens, providing invaluable insights into the molecular mechanisms underlying infectious diseases. The current ELM release includes 317 motif classes incorporating 3934 individual motif instances manually curated from 3867 scientific publications. ELM is available at: http://elm.eu.org.


Subject(s)
Communicable Diseases/genetics , Databases, Protein , Host-Pathogen Interactions/genetics , Protein Interaction Domains and Motifs , Software , Actin Cytoskeleton/chemistry , Actin Cytoskeleton/metabolism , Animals , Binding Sites , Cell Cycle/genetics , Cell Membrane/chemistry , Cell Membrane/metabolism , Communicable Diseases/metabolism , Communicable Diseases/virology , Cyclins/chemistry , Cyclins/genetics , Cyclins/metabolism , Eukaryotic Cells/cytology , Eukaryotic Cells/metabolism , Eukaryotic Cells/virology , Gene Expression Regulation , Humans , Integrins/chemistry , Integrins/genetics , Integrins/metabolism , Mice , Molecular Sequence Annotation , Protein Binding , Rats , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Signal Transduction , Transport Vesicles/chemistry , Transport Vesicles/metabolism , Viruses/genetics , Viruses/metabolism
2.
Int J Mol Sci ; 22(22)2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1534086

ABSTRACT

Transmembrane proteins (TMPs) play important roles in cells, ranging from transport processes and cell adhesion to communication. Many of these functions are mediated by intrinsically disordered regions (IDRs), flexible protein segments without a well-defined structure. Although a variety of prediction methods are available for predicting IDRs, their accuracy is very limited on TMPs due to their special physico-chemical properties. We prepared a dataset containing membrane proteins exclusively, using X-ray crystallography data. MemDis is a novel prediction method, utilizing convolutional neural network and long short-term memory networks for predicting disordered regions in TMPs. In addition to attributes commonly used in IDR predictors, we defined several TMP specific features to enhance the accuracy of our method further. MemDis achieved the highest prediction accuracy on TMP-specific dataset among other popular IDR prediction methods.


Subject(s)
Computational Biology/methods , Intrinsically Disordered Proteins/chemistry , Membrane Proteins/chemistry , Neural Networks, Computer , Amino Acid Sequence , Data Mining/methods , Databases, Protein/statistics & numerical data , Internet , Models, Molecular , Protein Conformation , Reproducibility of Results
3.
Bioinformatics ; 2021 Jun 29.
Article in English | MEDLINE | ID: covidwho-1286554

ABSTRACT

MOTIVATION: Cell polarity refers to the asymmetric organization of cellular components in various cells. Epithelial cells are the best-known examples of polarized cells, featuring apical and basolateral membrane domains. Mounting evidence suggests that short linear motifs play a major role in protein trafficking to these domains, although the exact rules governing them are still elusive. RESULTS: In this study we prepared neural networks that capture recurrent patterns to classify transmembrane proteins localizing into apical and basolateral membranes. Asymmetric expression of drug transporters results in vectorial drug transport, governing the pharmacokinetics of numerous substances, yet the data on how proteins are sorted in epithelial cells is very scattered. The provided method may offer help to experimentalists to identify or better characterize molecular networks regulating the distribution of transporters or surface receptors (including viral entry receptors like that of COVID-19). AVAILABILITY: The prediction server PolarProtPred is available at http://polarprotpred.ttk.hu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

4.
J Mol Biol ; 433(11): 166705, 2021 05 28.
Article in English | MEDLINE | ID: covidwho-917347

ABSTRACT

Most cells in multicellular organisms are somehow asymmetric, polarized: maintaining separate membrane domains. Typical examples are the epithelial cells (apical-basal polarization), neurons (dendritic-axonal domains), or migratory cells (with a leading and a trailing edge). Here we present the most comprehensive database containing experimentally verified mammalian proteins that display polarized sorting or secretion, focusing on epithelial polarity. In addition to the source cells or tissues, homology-based inferences and transmembrane topology (if applicable) are all provided. PolarProtDb also offers a detailed interface displaying all information that may be relevant for trafficking: including post-translational modifications (glycosylations and phosphorylations), known or predicted short linear motifs conserved across orthologs, as well as potential interaction partners. Data on polarized sorting has so far been scattered across myriads of publications, hence difficult to access. This information can help researchers in several areas, such as scanning for potential entry points of viral agents like COVID-19. PolarProtDb shall be a useful resource to design future experiments as well as for comparative analyses. The database is available at http://polarprotdb.enzim.hu.


Subject(s)
Databases, Factual , Epithelial Cells/cytology , Epithelial Cells/metabolism , Membrane Proteins/metabolism , COVID-19/metabolism , COVID-19/virology , Cell Movement/physiology , Cell Polarity/physiology , Genes , Glycosylation , Host Microbial Interactions , Humans , Phosphorylation , Protein Interaction Maps , Protein Transport , Proteome , SARS-CoV-2/metabolism
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