| Autor: |
Christophe Rouillon, Niels Schneberger, Haotian Chi, Katja Blumenstock, Stefano Da Vela, Katrin Ackermann, Jonas Moecking, Martin F. Peter, Wolfgang Boenigk, Reinhard Seifert, Bela E. Bode, Jonathan L. Schmid-Burgk, Dmitri Svergun, Matthias Geyer, Malcolm F. White, Gregor Hagelueken |
| Přispěvatelé: |
European Research Council, University of St Andrews. School of Biology, University of St Andrews. School of Chemistry, University of St Andrews. Institute of Behavioural and Neural Sciences, University of St Andrews. EaSTCHEM, University of St Andrews. Biomedical Sciences Research Complex, University of St Andrews. Centre of Magnetic Resonance, University of St Andrews. St Andrews Bioinformatics Unit |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature |
| Popis: |
Funding information: M.G. and J.L.S.B. are funded by the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy–EXC2151–390873048. M.F.W. acknowledges a European Research Council Advanced Grant (grant number 101018608) and the China Scholarship Council (REF: 202008420207 to H.C.). G.H. is grateful for funding by the Deutsche Forschungsgemeinschaft (grant number HA6805/6-1). CRISPR defense systems such as the well-known DNA-targeting Cas9 and the RNA-targeting type III systems are widespread in prokaryotes1,2. The latter can orchestrate a complex antiviral response that is initiated by the synthesis of cyclic oligoadenylates (cOAs) upon foreign RNA recognition3-5. Among a large set of proteins that were linked to type III systems and predicted to bind cOAs6,7, a CRISPR associated Lon protease (CalpL) stood out to us. The protein contains a sensor domain of the SAVED (SMODS-associated and fused to various effector domains) family7, fused to a Lon protease effector domain. However, the mode of action of this effector was unknown. Here, we report the structure and function of CalpL and show that the soluble protein forms a stable tripartite complex with two further proteins, CalpT and CalpS, that are encoded in the same operon. Upon activation by cA4, CalpL oligomerizes and specifically cleaves the MazF-homolog CalpT, releasing the extracytoplasmic function (ECF) sigma factor CalpS from the complex. This provides a direct connection between CRISPR-based foreign nucleic acid detection and transcriptional regulation. Furthermore, the presence of a cA4-binding SAVED domain in a CRISPR effector reveals an unexpected link to the cyclic oligonucleotide-based antiphage signaling system (CBASS). Postprint |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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