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The M2-1 protein of human metapneumovirus (HMPV) is a zinc-binding transcription antiterminator which is highly conserved among pneumoviruses. We report the structure of tetrameric HMPV M2-1. Each protomer features a N-terminal zinc finger domain and an α-helical tetramerization motif forming a rigid unit, followed by a flexible linker and an α-helical core domain. The tetramer is asymmetric, three of the protomers exhibiting a closed conformation, and one an open conformation. Molecular dynamics simulations and SAXS demonstrate a dynamic equilibrium between open and closed conformations in solution. Structures of adenosine monophosphate- and DNA- bound M2-1 establish the role of the zinc finger domain in base-specific recognition of RNA. Binding to 'gene end' RNA sequences stabilized the closed conformation of M2-1 leading to a drastic shift in the conformational landscape of M2-1. We propose a model for recognition of gene end signals and discuss the implications of these findings for transcriptional regulation in pneumoviruses.DOI: http://dx.doi.org/10.7554/eLife.02674.001.

Original publication

DOI

10.7554/eLife.02674

Type

Journal article

Journal

Elife

Publication Date

19/05/2014

Volume

3

Keywords

RNA polymerase, human metapneumovirus, structural virology, virus transcription, Adenosine Monophosphate, Amino Acid Sequence, Crystallography, X-Ray, DNA, Edetic Acid, Humans, Metapneumovirus, Molecular Dynamics Simulation, Molecular Sequence Data, Protein Binding, Protein Conformation, Protein Multimerization, Protein Stability, Protein Subunits, RNA, Viral, Scattering, Small Angle, Solutions, Solvents, Transcription, Genetic, Viral Proteins, Zinc Fingers