1. Structural Biology and Molecular Biophysics
  2. Microbiology and Infectious Disease
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Drastic changes in conformational dynamics of the antiterminator M2-1 regulate transcription efficiency in Pneumovirinae

  1. Cedric Leyrat
  2. Max Renner
  3. Karl Harlos
  4. Juha T Huiskonen
  5. Jonathan M Grimes  Is a corresponding author
  1. Wellcome Trust Centre for Human Genetics, United Kingdom
Research Article
  • Cited 25
  • Views 1,576
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Cite this article as: eLife 2014;3:e02674 doi: 10.7554/eLife.02674

Abstract

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.

Article and author information

Author details

  1. Cedric Leyrat

    Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Max Renner

    Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Karl Harlos

    Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Juha T Huiskonen

    Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Jonathan M Grimes

    Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom
    For correspondence
    jonathan@strubi.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Received: February 28, 2014
  2. Accepted: May 15, 2014
  3. Accepted Manuscript published: May 19, 2014 (version 1)
  4. Version of Record published: June 10, 2014 (version 2)

Copyright

© 2014, Leyrat et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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