Drastic changes in conformational dynamics of the antiterminator M2-1 regulate transcription efficiency in Pneumovirinae

Journal article

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.

Authors: Leyrat, C; Renner, M; Harlos, K; Huiskonen, J; Grimes, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: eLife Sciences Publications
• Journal: eLife
• Volume: 2014
• Issue: 3
• Article number: e02674
• Publication date: 2014-06-10
• Acceptance date: 2014-05-15
• DOI: 10.7554/elife.02674
• EISSN: 2050-084X
• Language: English
• Keywords: structural virology; human metapneumovirus; RNA polymerase; FFR; virus transcription