Tanner, S, Ariza, A, Richard, CA et al. (12 more authors) (2014) Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation. Proceedings of the National Academy of Sciences, 111 (4). pp. 1580-1585. ISSN 0027-8424
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Biopolymers; Crystallography, X-Ray; Humans; Nuclear Magnetic Resonance, Biomolecular; Phosphorylation; Protein Conformation; RNA; Respiratory Syncytial Viruses; Viral Proteins |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Crystallography (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Synthetic Biology (Leed) |
Depositing User: | Symplectic Publications |
Date Deposited: | 23 Mar 2015 13:46 |
Last Modified: | 04 Dec 2020 13:00 |
Published Version: | http://dx.doi.org/10.1073/pnas.1317262111 |
Status: | Published |
Publisher: | National Academy of Sciences |
Identification Number: | 10.1073/pnas.1317262111 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:83786 |