Viral and Cellular Proteins Containing FGDF Motifs Bind G3BP to Block Stress Granule Formation

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Stress granules (SGs) are dynamic aggregates of proteins and translationally silenced mRNA that are formed in cells upon various stress conditions, such as virus infection. SGs are thought to be antiviral, and many viruses have hence evolved countermeasures to prevent their formation, often targeting the essential SG protein G3BP. Here, we show that several otherwise unrelated viral and cellular proteins all bind G3BP with the sequence motif FGDF, and thereby repress SG formation: the non-structural protein 3 (nsP3) of the Old World alphavirus Semliki Forest virus (a close relative of the emerging, highly pathogenic Chikungunya virus); the protein ICP8 of herpes simplex virus; and in addition, the cellular protein USP10 (an SG component and protein deubiquitinase that stabilises e.g. the tumor suppressor p53). In this work, we also present and validate a model of the three-dimensional structure of G3BP bound to an FGDF-containing peptide. The FGDF-mediated G3BP binding represents an attractive target for therapeutic interventions against a range of diverse viral infections, and may also regulate the p53-stabilising function of USP10 in cancers.

Vyšlo v časopise: Viral and Cellular Proteins Containing FGDF Motifs Bind G3BP to Block Stress Granule Formation. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004659
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004659

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