Full-length three-dimensional structure of the influenza A virus M1 protein and its organization into a matrix layer.
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-...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-09-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3000827 |
| _version_ | 1811314466997927936 |
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| author | Lisa Selzer Zhaoming Su Grigore D Pintilie Wah Chiu Karla Kirkegaard |
| author_facet | Lisa Selzer Zhaoming Su Grigore D Pintilie Wah Chiu Karla Kirkegaard |
| author_sort | Lisa Selzer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T11:12:09Z |
| format | Article |
| id | doaj.art-5ec978df7f4f440b962d59a0df3d9f1c |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-13T11:12:09Z |
| publishDate | 2020-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-5ec978df7f4f440b962d59a0df3d9f1c2022-12-22T02:49:05ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852020-09-01189e300082710.1371/journal.pbio.3000827Full-length three-dimensional structure of the influenza A virus M1 protein and its organization into a matrix layer.Lisa SelzerZhaoming SuGrigore D PintilieWah ChiuKarla KirkegaardMatrix 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.https://doi.org/10.1371/journal.pbio.3000827 |
| spellingShingle | Lisa Selzer Zhaoming Su Grigore D Pintilie Wah Chiu Karla Kirkegaard Full-length three-dimensional structure of the influenza A virus M1 protein and its organization into a matrix layer. PLoS Biology |
| title | Full-length three-dimensional structure of the influenza A virus M1 protein and its organization into a matrix layer. |
| title_full | Full-length three-dimensional structure of the influenza A virus M1 protein and its organization into a matrix layer. |
| title_fullStr | Full-length three-dimensional structure of the influenza A virus M1 protein and its organization into a matrix layer. |
| title_full_unstemmed | Full-length three-dimensional structure of the influenza A virus M1 protein and its organization into a matrix layer. |
| title_short | Full-length three-dimensional structure of the influenza A virus M1 protein and its organization into a matrix layer. |
| title_sort | full length three dimensional structure of the influenza a virus m1 protein and its organization into a matrix layer |
| url | https://doi.org/10.1371/journal.pbio.3000827 |
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