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Title | Full-length three-dimensional structure of the influenza A virus M1 protein and its organization into a matrix layer. |
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Journal, issue, pages | PLoS Biol, Vol. 18, Issue 9, Page e3000827, Year 2020 |
Publish date | Sep 30, 2020 |
![]() | Lisa Selzer / Zhaoming Su / Grigore D Pintilie / Wah Chiu / Karla Kirkegaard / ![]() ![]() |
PubMed Abstract | 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 ...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. |
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Methods | EM (helical sym.) |
Resolution | 3.4 Å |
Structure data | EMDB-22384, PDB-7jm3: |
Source |
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![]() | VIRAL PROTEIN / influenza A / virus / matrix layer / M1 protein |