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TitleFull-length three-dimensional structure of the influenza A virus M1 protein and its organization into a matrix layer.
Journal, issue, pagesPLoS Biol, Vol. 18, Issue 9, Page e3000827, Year 2020
Publish dateSep 30, 2020
AuthorsLisa Selzer / Zhaoming Su / Grigore D Pintilie / Wah Chiu / Karla Kirkegaard /
PubMed AbstractMatrix proteins are encoded by many enveloped viruses, including influenza viruses, herpes viruses, and coronaviruses. Underneath the viral envelope of influenza virus, matrix protein 1 (M1) forms an ...Matrix proteins are encoded by many enveloped viruses, including influenza viruses, herpes viruses, and coronaviruses. Underneath the viral envelope of influenza virus, matrix protein 1 (M1) forms an oligomeric layer critical for particle stability and pH-dependent RNA genome release. However, high-resolution structures of full-length monomeric M1 and the matrix layer have not been available, impeding antiviral targeting and understanding of the pH-dependent transitions involved in cell entry. Here, purification and extensive mutagenesis revealed protein-protein interfaces required for the formation of multilayered helical M1 oligomers similar to those observed in virions exposed to the low pH of cell entry. However, single-layered helical oligomers with biochemical and ultrastructural similarity to those found in infectious virions before cell entry were observed upon mutation of a single amino acid. The highly ordered structure of the single-layered oligomers and their likeness to the matrix layer of intact virions prompted structural analysis by cryo-electron microscopy (cryo-EM). The resulting 3.4-Å-resolution structure revealed the molecular details of M1 folding and its organization within the single-shelled matrix. The solution of the full-length M1 structure, the identification of critical assembly interfaces, and the development of M1 assembly assays with purified proteins are crucial advances for antiviral targeting of influenza viruses.
External linksPLoS Biol / PubMed:32997652 / PubMed Central
MethodsEM (helical sym.)
Resolution3.4 Å
Structure data

EMDB-22384, PDB-7jm3:
Full-length three-dimensional structure of the influenza A virus M1 protein and its organization into a matrix layer
Method: EM (helical sym.) / Resolution: 3.4 Å

Source
  • Influenza A virus (A/Puerto Rico/8/1934(H1N1))
  • influenza a virus (strain a/puerto rico/8/1934 h1n1)
KeywordsVIRAL PROTEIN / influenza A / virus / matrix layer / M1 protein

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