PDBsum entry 4c3e

Viral protein

PDB id: 4c3e

Contents

Protein chains

(+ 3 more) 172 a.a.

(+ 1 more) 160 a.a.

Metals

_ZN ×16

Waters ×395

References listed in PDB file

Key reference

• Title: Crystal structure of the essential transcription antiterminator m2-1 protein of human respiratory syncytial virus and implications of its phosphorylation.
• Authors: S.J.Tanner, A.Ariza, C.A.Richard, H.F.Kyle, R.L.Dods, M.L.Blondot, W.Wu, J.Trincão, C.H.Trinh, J.A.Hiscox, M.W.Carroll, N.J.Silman, J.F.Eléouët, T.A.Edwards, J.N.Barr.
• Ref.: Proc Natl Acad Sci U S A, 2014, 111, 1580-1585. [DOI no: 10.1073/pnas.1317262111]
• PubMed id: 24434552

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.