دورية أكاديمية
أعرض في EDS

Type III CRISPR-Cas systems produce cyclic oligoadenylate second messengers.

التفاصيل البيبلوغرافية
العنوان: Type III CRISPR-Cas systems produce cyclic oligoadenylate second messengers.
المؤلفون: Niewoehner O; Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland., Garcia-Doval C; Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland., Rostøl JT; Laboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, New York 10065-6399, USA., Berk C; Department of Chemistry and Applied Biosciences, Institute for Pharmaceutical Sciences, Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland., Schwede F; BIOLOG Life Science Institute GmbH, Flughafendamm 9a, D-28199 Bremen, Germany., Bigler L; Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland., Hall J; Department of Chemistry and Applied Biosciences, Institute for Pharmaceutical Sciences, Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland., Marraffini LA; Laboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, New York 10065-6399, USA., Jinek M; Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
المصدر: Nature [Nature] 2017 Aug 31; Vol. 548 (7669), pp. 543-548. Date of Electronic Publication: 2017 Jul 19.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: CRISPR-Associated Proteins/*metabolism , CRISPR-Cas Systems/*genetics , Second Messenger Systems/*genetics , Second Messenger Systems/*physiology, Allosteric Regulation ; Diffusion ; Enzyme Activation ; Euryarchaeota/enzymology ; Euryarchaeota/genetics ; Immunity, Innate ; Protein Domains/genetics ; Ribonucleases/metabolism ; Thermus thermophilus/enzymology ; Thermus thermophilus/genetics
مستخلص: In many prokaryotes, type III clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated (Cas) systems detect and degrade invasive genetic elements by an RNA-guided, RNA-targeting multisubunit interference complex. The CRISPR-associated protein Csm6 additionally contributes to interference by functioning as a standalone RNase that degrades invader RNA transcripts, but the mechanism linking invader sensing to Csm6 activity is not understood. Here we show that Csm6 proteins are activated through a second messenger generated by the type III interference complex. Upon target RNA binding by the interference complex, its Cas10 subunit converts ATP into a cyclic oligoadenylate product, which allosterically activates Csm6 by binding to its CRISPR-associated Rossmann fold (CARF) domain. CARF domain mutations that abolish allosteric activation inhibit Csm6 activity in vivo, and mutations in the Cas10 Palm domain phenocopy loss of Csm6. Together, these results point to an unprecedented mechanism for regulation of CRISPR interference that bears striking conceptual similarity to oligoadenylate signalling in mammalian innate immunity.
التعليقات: Comment in: Nature. 2017 Aug 31;548(7669):527-528. (PMID: 28783729)
Comment in: Nat Chem Biol. 2017 Aug 18;13(9):923. (PMID: 28820872)
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معلومات مُعتمدة: 1DP2AI104556-01 United States NH NIH HHS; United States HHMI Howard Hughes Medical Institute
المشرفين على المادة: 0 (CRISPR-Associated Proteins)
EC 3.1.- (Ribonucleases)
تواريخ الأحداث: Date Created: 20170720 Date Completed: 20171214 Latest Revision: 20181113
رمز التحديث: 20240628
DOI: 10.1038/nature23467
PMID: 28722012
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/nature23467