Structural and molecular basis for Cardiovirus 2A protein as a viral gene expression switch.
Authors
Pekarek, Lukas
Publication Date
2021-12-09Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
12
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Hill, C. H., Pekarek, L., Napthine, S., Kibe, A., Firth, A., Graham, S., Caliskan, N., & et al. (2021). Structural and molecular basis for Cardiovirus 2A protein as a viral gene expression switch.. Nat Commun, 12 (1) https://doi.org/10.1038/s41467-021-27400-7
Description
Funder: Helmholtz Association; doi: https://doi.org/10.13039/501100009318
Abstract
Programmed -1 ribosomal frameshifting (PRF) in cardioviruses is activated by the 2A protein, a multi-functional virulence factor that also inhibits cap-dependent translational initiation. Here we present the X-ray crystal structure of 2A and show that it selectively binds to a pseudoknot-like conformation of the PRF stimulatory RNA element in the viral genome. Using optical tweezers, we demonstrate that 2A stabilises this RNA element, likely explaining the increase in PRF efficiency in the presence of 2A. Next, we demonstrate a strong interaction between 2A and the small ribosomal subunit and present a cryo-EM structure of 2A bound to initiated 70S ribosomes. Multiple copies of 2A bind to the 16S rRNA where they may compete for binding with initiation and elongation factors. Together, these results define the structural basis for RNA recognition by 2A, show how 2A-mediated stabilisation of an RNA pseudoknot promotes PRF, and reveal how 2A accumulation may shut down translation during virus infection.
Keywords
Article, /631/45/500, /631/326/596, /631/337/574/1789, /631/535/1258/1259, /631/535/1266, /101/28, /82/83, /82/80, /145, /82/29, /38/71, /38/90, /82/16, article
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/D009499/1)
Wellcome Trust (202797/Z/16/Z)
Wellcome Trust (098406/Z/12/Z)
Wellcome Trust (098406/Z/12/B)
Wellcome Trust (106207/Z/14/Z)
European Research Council (646891)
Identifiers
s41467-021-27400-7, 27400
External DOI: https://doi.org/10.1038/s41467-021-27400-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/331852
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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