4C3E

HRSV M2-1 mutant S58D S61D, P21 crystal

Summary for 4C3E

• Entry DOI: 10.2210/pdb4c3e/pdb
• Related: 4C3B 4C3D
• Descriptor: MATRIX M2-1, ZINC ION (3 entities in total)
• Functional Keywords: viral protein
• Biological source: HUMAN RESPIRATORY SYNCYTIAL VIRUS
• Cellular location: Virion (Potential): P04545
• Total number of polymer chains: 16
• Total formula weight: 363571.33

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

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: 24434552
DOI: 10.1073/PNAS.1317262111

Experimental method

X-RAY DIFFRACTION (2.4 Å)