TY - JOUR TI - Drastic changes in conformational dynamics of the antiterminator M2-1 regulate transcription efficiency in Pneumovirinae AU - Leyrat, Cedric AU - Renner, Max AU - Harlos, Karl AU - Huiskonen, Juha T AU - Grimes, Jonathan M A2 - Dötsch, Volker VL - 3 PY - 2014 DA - 2014/05/19 SP - e02674 C1 - eLife 2014;3:e02674 DO - 10.7554/eLife.02674 UR - https://doi.org/10.7554/eLife.02674 AB - 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. KW - human metapneumovirus KW - virus transcription KW - RNA polymerase KW - structural virology JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -