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

DOI: 10.7554/eLife.12627 DOI Help
PMID: 26880565 PMID Help

Authors: Max Renner (University of Oxford) , Mattia Bertinelli (University of Oxford) , Cedric Leyrat (University of Oxford) , G. C. Paesen (University of Oxford) , Laura Freitas Saraiva De Oliveira (University of Oxford) , Juha Huiskonen (University of Oxford) , Jonathan Grimes (Division of Structural Biology, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife , VOL 5

State: Published (Approved)
Published: February 2016
Diamond Proposal Number(s): 8423

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

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