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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.
Nat Commun ; 12(1): 6761, 2021 11 19.
Article in English | MEDLINE | ID: covidwho-1526072

ABSTRACT

Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a viral peptide discovery approach covering 23 coronavirus strains that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an ΦxFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its ΦxFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction dampened SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents.


Subject(s)
Integration Host Factors/metabolism , SARS-CoV-2/metabolism , Adaptor Proteins, Signal Transducing/metabolism , DNA Helicases/metabolism , Humans , Poly-ADP-Ribose Binding Proteins/metabolism , RNA Helicases/metabolism , RNA Recognition Motif Proteins/metabolism , RNA-Binding Proteins/metabolism , Virus Replication/physiology
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