Kingston, N.J., Snowden, J.S., Grehan, K. orcid.org/0000-0003-3976-756X et al. (8 more authors) (2024) Mechanism of enterovirus VP0 maturation cleavage based on the structure of a stabilised assembly intermediate. PLOS Pathogens, 20 (9). e1012511. ISSN 1553-7366
Abstract
Molecular details of genome packaging are little understood for the majority of viruses. In enteroviruses (EVs), cleavage of the structural protein VP0 into VP4 and VP2 is initiated by the incorporation of RNA into the assembling virion and is essential for infectivity. We have applied a combination of bioinformatic, molecular and structural approaches to generate the first high-resolution structure of an intermediate in the assembly pathway, termed a provirion, which contains RNA and intact VP0. We have demonstrated an essential role of VP0 E096 in VP0 cleavage independent of RNA encapsidation and generated a new model of capsid maturation, supported by bioinformatic analysis. This provides a molecular basis for RNA-dependence, where RNA induces conformational changes required for VP0 maturation, but that RNA packaging itself is not sufficient to induce maturation. These data have implications for understanding production of infectious virions and potential relevance for future vaccine and antiviral drug design.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Editors: |
|
Copyright, Publisher and Additional Information: | © 2024 Kingston et al. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Molecular Virology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 14 Oct 2024 09:45 |
Last Modified: | 14 Oct 2024 09:45 |
Status: | Published |
Publisher: | Public Library of Science |
Identification Number: | 10.1371/journal.ppat.1012511 |
Related URLs: | |
Sustainable Development Goals: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:218299 |