Drastic changes in conformational dynamics of the antiterminator M2-1 regulate transcription efficiency in Pneumovirinae.
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.
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
Cedric
C
Leyrat
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
Max
M
Renner
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
Karl
K
Harlos
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
Juha T
JT
Huiskonen
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom Diamond Light Source Ltd, Didcot, United Kingdom jonathan@strubi.ox.ac.uk.
Jonathan M
JM
Grimes
D000249:Adenosine Monophosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D029121:Metapneumovirus / Q000235:genetics*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D055550:Protein Stability; D021122:Protein Subunits / Q000737:chemistry; D012367:RNA, Viral / Q000378:metabolism / Q000648:ultrastructure; D053838:Scattering, Small Angle; D012996:Solutions; D012997:Solvents; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D016335:Zinc Fingers
D021122:Protein Subunits; D012367:RNA, Viral; D012996:Solutions; D012997:Solvents; D014764:Viral Proteins; D000249:Adenosine Monophosphate; D004247:DNA; D004492:Edetic Acid
RNA polymerase; human metapneumovirus; structural virology; virus transcription