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dc.contributor.authorGrüschow, Sabine
dc.contributor.authorMcQuarrie, Stuart
dc.contributor.authorAckermann, Katrin
dc.contributor.authorMcMahon, Stephen
dc.contributor.authorBode, Bela E
dc.contributor.authorGloster, Tracey M
dc.contributor.authorWhite, Malcolm F
dc.date.accessioned2024-03-15T12:30:13Z
dc.date.available2024-03-15T12:30:13Z
dc.date.issued2024-04-12
dc.identifier300250146
dc.identifierb54444d3-2eef-4e70-8940-57d3ff5c8c7b
dc.identifier85190494090
dc.identifier38471818
dc.identifier.citationGrüschow , S , McQuarrie , S , Ackermann , K , McMahon , S , Bode , BE , Gloster , TM & White , MF 2024 , ' CRISPR antiphage defence mediated by the cyclic nucleotide-binding membrane protein Csx23 ' , Nucleic Acids Research , vol. 52 , no. 6 , gkae167 , pp. 2761-2775 . https://doi.org/10.1093/nar/gkae167en
dc.identifier.issn0305-1048
dc.identifier.otherRIS: urn:4FED0C00067E7BC8F42D7184FCF23318
dc.identifier.otherORCID: /0000-0002-3384-271X/work/155626529
dc.identifier.otherORCID: /0000-0003-4828-4842/work/155627282
dc.identifier.otherORCID: /0000-0003-1543-9342/work/155627316
dc.identifier.urihttps://hdl.handle.net/10023/29505
dc.descriptionFunding: Biotechnology and Biological Sciences Research Council [BB/T004789/1 to M.F.W., T.M.G.]; European Research Council Advanced Grant [101018608 to M.F.W.]; Engineering and Physical Sciences Research Council [EP/X016455/1 to K.A., B.E.B., M.F.W.]; BBSRC equipment grants [BB/R013780/1, BB/T017740/1 to B.E.B.]. Funding for open access charge: University of St Andrews block grant.en
dc.description.abstractCRISPR-Cas provides adaptive immunity in prokaryotes. Type III CRISPR systems detect invading RNA and activate the catalytic Cas10 subunit, which generates a range of nucleotide second messengers to signal infection. These molecules bind and activate a diverse range of effector proteins that provide immunity by degrading viral components and/or by disturbing key aspects of cellular metabolism to slow down viral replication. Here, we focus on the uncharacterised effector Csx23, which is widespread in Vibrio cholerae. Csx23 provides immunity against plasmids and phage when expressed in Escherichia coli along with its cognate type III CRISPR system. The Csx23 protein localises in the membrane using an N-terminal transmembrane α-helical domain and has a cytoplasmic C-terminal domain that binds cyclic tetra-adenylate (cA4), activating its defence function. Structural studies reveal a tetrameric structure with a novel fold that binds cA4 specifically. Using pulse EPR, we demonstrate that cA4 binding to the cytoplasmic domain of Csx23 results in a major perturbation of the transmembrane domain, consistent with the opening of a pore and/or disruption of membrane integrity. This work reveals a new class of cyclic nucleotide binding protein and provides key mechanistic detail on a membrane-associated CRISPR effector.
dc.format.extent15
dc.format.extent3111357
dc.language.isoeng
dc.relation.ispartofNucleic Acids Researchen
dc.subjectGeneticsen
dc.subjectDASen
dc.subjectMCCen
dc.titleCRISPR antiphage defence mediated by the cyclic nucleotide-binding membrane protein Csx23en
dc.typeJournal articleen
dc.contributor.sponsorBBSRCen
dc.contributor.sponsorEPSRCen
dc.contributor.sponsorBBSRCen
dc.contributor.sponsorBBSRCen
dc.contributor.sponsorEuropean Research Councilen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews. Centre of Magnetic Resonanceen
dc.contributor.institutionUniversity of St Andrews. St Andrews Bioinformatics Uniten
dc.identifier.doi10.1093/nar/gkae167
dc.description.statusPeer revieweden
dc.identifier.grantnumberBB/T004789/1en
dc.identifier.grantnumberEP/X016455/1en
dc.identifier.grantnumberBB/R013780/1en
dc.identifier.grantnumberBB/T017740/1en
dc.identifier.grantnumber01018608en


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