Packaging signals in single-stranded RNA viruses: nature’s alternative to a purely electrostatic assembly mechanism

Stockley, P.G. et al. (2013) Packaging signals in single-stranded RNA viruses: nature’s alternative to a purely electrostatic assembly mechanism. Journal of Biological Physics, 39(2), pp. 277-287. (doi: 10.1007/s10867-013-9313-0)

[img]
Preview
Text
82148 (1).pdf - Cover Image

62kB
[img]
Preview
Text
82148.pdf - Published Version

778kB

Abstract

The formation of a protective protein container is an essential step in the life-cycle of most viruses. In the case of single-stranded (ss)RNA viruses, this step occurs in parallel with genome packaging in a co-assembly process. Previously, it had been thought that this process can be explained entirely by electrostatics. Inspired by recent single-molecule fluorescence experiments that recapitulate the RNA packaging specificity seen in vivo for two model viruses, we present an alternative theory, which recognizes the important cooperative roles played by RNA–coat protein interactions, at sites we have termed packaging signals. The hypothesis is that multiple copies of packaging signals, repeated according to capsid symmetry, aid formation of the required capsid protein conformers at defined positions, resulting in significantly enhanced assembly efficiency. The precise mechanistic roles of packaging signal interactions may vary between viruses, as we have demonstrated for MS2 and STNV. We quantify the impact of packaging signals on capsid assembly efficiency using a dodecahedral model system, showing that heterogeneous affinity distributions of packaging signals for capsid protein out-compete those of homogeneous affinities. These insights pave the way to a new anti-viral therapy, reducing capsid assembly efficiency by targeting of the vital roles of the packaging signals, and opens up new avenues for the efficient construction of protein nanocontainers in bionanotechnology.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bakker, Dr Saskia
Authors: Stockley, P.G., Twarock, R., Bakker, S.E., Barker, A.M., Borodavka, A., Dykeman, E., Ford, R.J., Pearson, A.R., Phillips, S.E.V., Ranson, N.A., and Tuma, R.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Biological Physics
Publisher:Springer Verlag
ISSN:0092-0606
ISSN (Online):1573-0689
Copyright Holders:Copyright © 2013 Springer-Verlag
First Published:First published in Journal of Biological Physics 39(2):277-287
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record