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dc.contributor.authorHill, Chris H
dc.contributor.authorPekarek, Lukas
dc.contributor.authorNapthine, Sawsan
dc.contributor.authorKibe, Anuja
dc.contributor.authorFirth, Andrew
dc.contributor.authorGraham, Stephen
dc.contributor.authorCaliskan, Neva
dc.contributor.authorBrierley, Ian
dc.date.accessioned2022-01-04T12:00:38Z
dc.date.available2022-01-04T12:00:38Z
dc.date.issued2021-12-09
dc.date.submitted2021-02-19
dc.identifier.issn2041-1723
dc.identifier.others41467-021-27400-7
dc.identifier.other27400
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331852
dc.descriptionFunder: Helmholtz Association; doi: https://doi.org/10.13039/501100009318
dc.description.abstractProgrammed -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.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/45/500
dc.subject/631/326/596
dc.subject/631/337/574/1789
dc.subject/631/535/1258/1259
dc.subject/631/535/1266
dc.subject/101/28
dc.subject/82/83
dc.subject/82/80
dc.subject/145
dc.subject/82/29
dc.subject/38/71
dc.subject/38/90
dc.subject/82/16
dc.subjectarticle
dc.titleStructural and molecular basis for Cardiovirus 2A protein as a viral gene expression switch.
dc.typeArticle
dc.date.updated2022-01-04T12:00:21Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume12
dc.identifier.doi10.17863/CAM.79302
dcterms.dateAccepted2021-11-12
rioxxterms.versionofrecord10.1038/s41467-021-27400-7
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidHill, Chris H [0000-0001-7037-0611]
dc.contributor.orcidNapthine, Sawsan [0000-0001-7404-8494]
dc.contributor.orcidKibe, Anuja [0000-0001-8547-785X]
dc.contributor.orcidFirth, Andrew [0000-0002-7986-9520]
dc.contributor.orcidGraham, Stephen [0000-0003-4547-4034]
dc.contributor.orcidCaliskan, Neva [0000-0003-0435-4757]
dc.contributor.orcidBrierley, Ian [0000-0003-3965-4370]
dc.identifier.eissn2041-1723
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/D009499/1)
pubs.funder-project-idWellcome Trust (202797/Z/16/Z)
pubs.funder-project-idWellcome Trust (098406/Z/12/Z)
pubs.funder-project-idWellcome Trust (098406/Z/12/B)
pubs.funder-project-idWellcome Trust (106207/Z/14/Z)
pubs.funder-project-idEuropean Research Council (646891)
cam.issuedOnline2021-12-09


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