4C3D
HRSV M2-1, P422 crystal form
Summary for 4C3D
Entry DOI | 10.2210/pdb4c3d/pdb |
Related | 4C3B 4C3E |
Descriptor | MATRIX M2-1, CADMIUM ION (3 entities in total) |
Functional Keywords | viral protein, m2-1 protein |
Biological source | HUMAN RESPIRATORY SYNCYTIAL VIRUS |
Cellular location | Virion (Potential): P04545 |
Total number of polymer chains | 2 |
Total formula weight | 45653.20 |
Authors | Tanner, S.J.,Ariza, A.,Richard, C.A.,Wu, W.,Trincao, J.,Hiscox, J.A.,Carroll, M.W.,Silman, N.J.,Eleouet, J.F.,Edwards, T.A.,Barr, J.N. (deposition date: 2013-08-22, release date: 2014-01-22, Last modification date: 2024-05-08) |
Primary citation | Tanner, S.J.,Ariza, A.,Richard, C.,Kyle, H.F.,Dods, R.L.,Blondot, M.,Wu, W.,Trincao, J.,Trinh, C.H.,Hiscox, J.A.,Carroll, M.W.,Silman, N.J.,Eleouet, J.,Edwards, T.A.,Barr, J.N. Crystal Structure of the Essential Transcription Antiterminator M2-1 Protein of Human Respiratory Syncytial Virus and Implications of its Phosphorylation. Proc.Natl.Acad.Sci.USA, 111:1580-, 2014 Cited by PubMed 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. PubMed: 24434552DOI: 10.1073/PNAS.1317262111 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.52 Å) |
Structure validation
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