PropertyValue
?:abstract
  • The interferon-inducible transmembrane (IFITM) proteins belong to the Dispanin/CD225 family and inhibit diverse virus infections. IFITM3 reduces membrane fusion between cells and virions through a poorly characterized mechanism. Mutation of proline-rich transmembrane protein 2 (PRRT2), a regulator of neurotransmitter release, at glycine-305 was previously linked to paroxysmal neurological disorders in humans. Here, we show that glycine-305 and the homologous site in IFITM3, glycine-95, drive protein oligomerization from within a GxxxG motif. Mutation of glycine-95 (and to a lesser extent, glycine-91) disrupted IFITM3 oligomerization and reduced its antiviral activity against Influenza A virus. An oligomerization-defective variant was used to reveal that IFITM3 promotes membrane rigidity in a glycine-95-dependent and amphipathic helix-dependent manner. Furthermore, a compound which counteracts virus inhibition by IFITM3, Amphotericin B, prevented the IFITM3-mediated rigidification of membranes. Overall, these data suggest that IFITM3 oligomers inhibit virus-cell fusion by promoting membrane rigidity.
is ?:annotates of
?:creator
?:doi
  • 10.7554/elife.58537
?:doi
?:journal
  • eLife
?:license
  • cc0
?:pdf_json_files
  • document_parses/pdf_json/50f8a0356508499df4f7d48b728c07dc2acb4828.json
?:pmc_json_files
  • document_parses/pmc_json/PMC7665892.xml.json
?:pmcid
?:pmid
?:pmid
  • 33112230.0
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:sha_id
?:source
  • Medline; PMC
?:title
  • Homology-guided identification of a conserved motif linking the antiviral functions of IFITM3 to its oligomeric state
?:type
?:year
  • 2020-10-28

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