Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation

Autor: Tanner, SJ, Ariza, A, Richard, CA, Kyle, HF, Dods, RL, Blondot, ML, Wu, W, Trincão, J, Trinh, CH, Hiscox, JA, Carroll, MW, Silman, NJ, Eléouët, JF, Edwards, TA, Barr, JN
Přispěvatelé: University of Leeds, Public Health England, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Institute of Infection and Global Health, University of Liverpool, Research Complex at Harwell, Public Health England and Biotechnology and Biological Sciences Research Council Collaborative award in Science and Engineering studentship, Agence Nationale de la Recherche, Wellcome Trust, Engineering and Physical Sciences Research Council, Astra Zeneca, University Research scholarship
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Proceedings of the National Academy of Sciences of the United States of America
Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2014, 111 (4), pp.1580-1585. ⟨10.1073/pnas.1317262111⟩
ISSN: 0027-8424
1091-6490
Popis: International audience; 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 angstrom. 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.
Databáze: OpenAIRE
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