Show simple item record

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.accessioned2021-11-18T00:30:20Z
dc.date.available2021-11-18T00:30:20Z
dc.date.issued2021-12-09
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330720
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.publisherSpringer Science and Business Media LLC
dc.rightsAll rights reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleStructural and molecular basis for Cardiovirus 2A protein as a viral gene expression switch.
dc.typeArticle
prism.publicationDate2021
prism.publicationNameNat Commun
dc.identifier.doi10.17863/CAM.78163
dcterms.dateAccepted2021-11-12
rioxxterms.versionofrecord10.1038/s41467-021-27400-7
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-11-16
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
rioxxterms.typeJournal Article/Review
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
cam.orpheus.success2021-11-17 - Embargo set during processing via Fast-track
rioxxterms.freetoread.startdate2021-11-16


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record