Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein

  1. Max Renner
  2. Mattia Bertinelli
  3. Cedric Leyrat
  4. Guido C Paesen
  5. Laura Freitas Saraiva de Oliveira
  6. Juha T Huiskonen
  7. Jonathan M Grimes  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. Wellcome Trust Centre for Human Genetics, United Kingdom

Abstract

Non-segmented, (-)RNA viruses cause serious human diseases. Human metapneumovirus (HMPV), an emerging pathogen of this order of viruses (Mononegavirales) is one of the main causes of respiratory tract illness in children. To help elucidate the assembly mechanism of the nucleocapsid (the viral RNA genome packaged by the nucleoprotein N) we present crystallographic structures of HMPV N in its assembled RNA-bound state and in a monomeric state, bound to the polymerase cofactor P. Our structures reveal molecular details of how P inhibits the self-assembly of N and how N transitions between the RNA-free and RNA-bound conformational state. Notably, we observe a role for the C-terminal extension of N in directly preventing premature uptake of RNA by inserting into the RNA-binding cleft.Our structures suggest a common mechanism of how the growth of the nucleocapsid is orchestrated, and highlight an interaction site representing an important target for antivirals.

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Author details

  1. Max Renner

    Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Mattia Bertinelli

    Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Cedric Leyrat

    Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Guido C Paesen

    Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Laura Freitas Saraiva de Oliveira

    Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Juha T Huiskonen

    Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Jonathan M Grimes

    Division of Structural Biology, 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.

Copyright

© 2016, Renner 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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  1. Max Renner
  2. Mattia Bertinelli
  3. Cedric Leyrat
  4. Guido C Paesen
  5. Laura Freitas Saraiva de Oliveira
  6. Juha T Huiskonen
  7. Jonathan M Grimes
(2016)
Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein
eLife 5:e12627.
https://doi.org/10.7554/eLife.12627

Share this article

https://doi.org/10.7554/eLife.12627

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