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dc.contributor.authorAthukoralage, Januka Sahan
dc.contributor.authorMcMahon, Stephen
dc.contributor.authorZhang, Changyi
dc.contributor.authorGruschow, Sabine
dc.contributor.authorGraham, Shirley
dc.contributor.authorKrupovic, Mart
dc.contributor.authorWhitaker, Rachel
dc.contributor.authorGloster, Tracey
dc.contributor.authorWhite, Malcolm
dc.date.accessioned2020-07-14T23:34:21Z
dc.date.available2020-07-14T23:34:21Z
dc.date.issued2020-01-23
dc.identifier.citationAthukoralage , J S , McMahon , S , Zhang , C , Gruschow , S , Graham , S , Krupovic , M , Whitaker , R , Gloster , T & White , M 2020 , ' An anti-CRISPR viral ring nuclease subverts type III CRISPR immunity ' , Nature , vol. 577 , no. 7791 , pp. 572-575 . https://doi.org/10.1038/s41586-019-1909-5en
dc.identifier.issn0028-0836
dc.identifier.otherPURE: 264190868
dc.identifier.otherPURE UUID: ce072acd-9b6c-45aa-b384-b78e01cb7f06
dc.identifier.otherWOS: 000509200100025
dc.identifier.otherORCID: /0000-0003-1543-9342/work/68280513
dc.identifier.otherORCID: /0000-0002-1666-0180/work/68281771
dc.identifier.otherWOS: 000509200100025
dc.identifier.otherScopus: 85078554373
dc.identifier.urihttp://hdl.handle.net/10023/20252
dc.descriptionThis work was supported by grants from the Biotechnology and Biological Sciences Research Council (BB/S000313/1 to M.F.W. and BB/R008035/1 to T.M.G.) and by a NASA Exobiology and Evolutionary Biology grant (NNX14AK23G to R.J.W.).en
dc.description.abstractThe CRISPR system in bacteria and archaea provides adaptive immunity against mobile genetic elements. Type III CRISPR systems detect viral RNA, resulting in the activation of two regions of the Cas10 protein: an HD nuclease domain (which degrades viral DNA)1,2 and a cyclase domain (which synthesizes cyclic oligoadenylates from ATP)3,4,5. Cyclic oligoadenylates in turn activate defence enzymes with a CRISPR-associated Rossmann fold domain6, sculpting a powerful antiviral response7,8,9,10 that can drive viruses to extinction7,8. Cyclic nucleotides are increasingly implicated in host–pathogen interactions11,12,13. Here we identify a new family of viral anti-CRISPR (Acr) enzymes that rapidly degrade cyclic tetra-adenylate (cA4). The viral ring nuclease AcrIII-1 is widely distributed in archaeal and bacterial viruses and in proviruses. The enzyme uses a previously unknown fold to bind cA4 specifically, and a conserved active site to rapidly cleave this signalling molecule, allowing viruses to neutralize the type III CRISPR defence system. The AcrIII-1 family has a broad host range, as it targets cA4 signalling molecules rather than specific CRISPR effector proteins. Our findings highlight the crucial role of cyclic nucleotide signalling in the conflict between viruses and their hosts.
dc.format.extent19
dc.language.isoeng
dc.relation.ispartofNatureen
dc.rightsCopyright © 2020 Springer Nature. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/xxxx/10.1038/s41586-019-1909-5en
dc.subjectSystemen
dc.subjectEvolutionaryen
dc.subjectMechanismen
dc.subjectSpaceen
dc.subjectDNAen
dc.subjectQH301 Biologyen
dc.subjectQR355 Virologyen
dc.subjectDASen
dc.subjectBDCen
dc.subjectR2Cen
dc.subject.lccQH301en
dc.subject.lccQR355en
dc.titleAn anti-CRISPR viral ring nuclease subverts type III CRISPR immunityen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1038/s41586-019-1909-5
dc.description.statusPeer revieweden
dc.date.embargoedUntil2020-07-15


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