Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation
The M2-1 protein of the important pathogen human respiratory syncytial virus is a zinc-binding transcription antiterminator that is essential for viral gene expression. We present the crystal structure of full-length M2-1 protein in its native tetrameric form at a resolution of 2.5 Å. The structure...
| मुख्य लेखकों: | , , , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
National Academy of Sciences
2014
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| _version_ | 1826298884511498240 |
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| author | Tanner, S Ariza, A Richard, C al., E |
| author_facet | Tanner, S Ariza, A Richard, C al., E |
| author_sort | Tanner, S |
| collection | OXFORD |
| description | The M2-1 protein of the important pathogen human respiratory syncytial virus is a zinc-binding transcription antiterminator that is essential for viral gene expression. We present the crystal structure of full-length M2-1 protein in its native tetrameric form at a resolution of 2.5 Å. The structure reveals that M2-1 forms a disk-like assembly with tetramerization driven by a long helix forming a four-helix bundle at its center, further stabilized by contact between the zinc-binding domain and adjacent protomers. The tetramerization helix is linked to a core domain responsible for RNA binding activity by a flexible region on which lie two functionally critical serine residues that are phosphorylated during infection. The crystal structure of a phosphomimetic M2-1 variant revealed altered charge density surrounding this flexible region although its position was unaffected. Structure-guided mutagenesis identified residues that contributed to RNA binding and antitermination activity, revealing a strong correlation between these two activities, and further defining the role of phosphorylation in M2-1 antitermination activity. The data we present here identify surfaces critical for M2-1 function that may be targeted by antiviral compounds. |
| first_indexed | 2024-03-07T04:53:35Z |
| format | Journal article |
| id | oxford-uuid:d5cdbc40-4e83-46db-9d08-f7a44f3f51a2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:53:35Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:d5cdbc40-4e83-46db-9d08-f7a44f3f51a22022-03-27T08:28:43ZCrystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d5cdbc40-4e83-46db-9d08-f7a44f3f51a2EnglishSymplectic Elements at OxfordNational Academy of Sciences2014Tanner, SAriza, ARichard, Cal., EThe M2-1 protein of the important pathogen human respiratory syncytial virus is a zinc-binding transcription antiterminator that is essential for viral gene expression. We present the crystal structure of full-length M2-1 protein in its native tetrameric form at a resolution of 2.5 Å. The structure reveals that M2-1 forms a disk-like assembly with tetramerization driven by a long helix forming a four-helix bundle at its center, further stabilized by contact between the zinc-binding domain and adjacent protomers. The tetramerization helix is linked to a core domain responsible for RNA binding activity by a flexible region on which lie two functionally critical serine residues that are phosphorylated during infection. The crystal structure of a phosphomimetic M2-1 variant revealed altered charge density surrounding this flexible region although its position was unaffected. Structure-guided mutagenesis identified residues that contributed to RNA binding and antitermination activity, revealing a strong correlation between these two activities, and further defining the role of phosphorylation in M2-1 antitermination activity. The data we present here identify surfaces critical for M2-1 function that may be targeted by antiviral compounds. |
| spellingShingle | Tanner, S Ariza, A Richard, C al., E Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation |
| title | Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation |
| title_full | Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation |
| title_fullStr | Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation |
| title_full_unstemmed | Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation |
| title_short | Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation |
| title_sort | crystal structure of the essential transcription antiterminator m2 1 protein of human respiratory syncytial virus and implications of its phosphorylation |
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