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

PDB id:

4c3e

Name:

Viral protein

Title:

Hrsv m2-1 mutant s58d s61d, p21 crystal

Structure:

Matrix m2-1. Chain: a, b, c, d, e, f, g, h, i, j, k, l, m, n, o, p. Synonym: envelope-associated 22 kda protein, hrsv m2-1. Engineered: yes. Mutation: yes

Source:

Human respiratory syncytial virus. Organism_taxid: 11259. Strain: a2. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: gold.

Resolution:

2.40Å R-factor: 0.205 R-free: 0.238

Authors:

S.J.Tanner,A.Ariza,C.A.Richard,W.Wu,J.Trincao,J.A.Hiscox,M.W.Carroll, N.J.Silman,J.F.Eleouet,T.A.Edwards,J.N.Barr

Key ref:

S.J.Tanner et al. (2014). Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation. Proc Natl Acad Sci U S A, 111, 1580-1585. PubMed id: 24434552 DOI: 10.1073/pnas.1317262111

Date:

22-Aug-13 Release date: 22-Jan-14

Protein chains

P04545  (M21_HRSVA) -  Protein M2-1 from Human respiratory syncytial virus A (strain A2)

Seq: 194 a.a.

Struc: 172 a.a.*

Protein chains

P04545  (M21_HRSVA) -  Protein M2-1 from Human respiratory syncytial virus A (strain A2)

Seq: 194 a.a.

Struc: 160 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P: E.C.?

DOI no: 10.1073/pnas.1317262111

Proc Natl Acad Sci U S A 111:1580-1585 (2014)

PubMed id: 24434552

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

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.

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.