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Tetramerisation of the CRISPR ring nuclease Crn3/Csx3 facilitates cyclic oligoadenylate cleavage.
Elife. 2020 Jun 29; 9E

Abstract

Type III CRISPR systems detect foreign RNA and activate the cyclase domain of the Cas10 subunit, generating cyclic oligoadenylate (cOA) molecules that act as a second messenger to signal infection, activating nucleases that degrade the nucleic acid of both invader and host. This can lead to dormancy or cell death; to avoid this, cells need a way to remove cOA from the cell once a viral infection has been defeated. Enzymes specialised for this task are known as ring nucleases, but are limited in their distribution. Here, we demonstrate that the widespread CRISPR associated protein Csx3, previously described as an RNA deadenylase, is a ring nuclease that rapidly degrades cyclic tetra-adenylate (cA4). The enzyme has an unusual cooperative reaction mechanism involving an active site that spans the interface between two dimers, sandwiching the cA4 substrate. We propose the name Crn3 (CRISPR associated ring nuclease 3) for the Csx3 family.

Authors+Show Affiliations

Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, United Kingdom.Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, United Kingdom.Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, United Kingdom.Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, United Kingdom.Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, United Kingdom.Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, United Kingdom.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32597755

Citation

Athukoralage, Januka S., et al. "Tetramerisation of the CRISPR Ring Nuclease Crn3/Csx3 Facilitates Cyclic Oligoadenylate Cleavage." ELife, vol. 9, 2020.
Athukoralage JS, McQuarrie S, Grüschow S, et al. Tetramerisation of the CRISPR ring nuclease Crn3/Csx3 facilitates cyclic oligoadenylate cleavage. Elife. 2020;9.
Athukoralage, J. S., McQuarrie, S., Grüschow, S., Graham, S., Gloster, T. M., & White, M. F. (2020). Tetramerisation of the CRISPR ring nuclease Crn3/Csx3 facilitates cyclic oligoadenylate cleavage. ELife, 9. https://doi.org/10.7554/eLife.57627
Athukoralage JS, et al. Tetramerisation of the CRISPR Ring Nuclease Crn3/Csx3 Facilitates Cyclic Oligoadenylate Cleavage. Elife. 2020 Jun 29;9 PubMed PMID: 32597755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tetramerisation of the CRISPR ring nuclease Crn3/Csx3 facilitates cyclic oligoadenylate cleavage. AU - Athukoralage,Januka S, AU - McQuarrie,Stuart, AU - Grüschow,Sabine, AU - Graham,Shirley, AU - Gloster,Tracey M, AU - White,Malcolm F, Y1 - 2020/06/29/ PY - 2020/04/06/received PY - 2020/06/28/accepted PY - 2020/7/1/pubmed PY - 2020/7/1/medline PY - 2020/6/30/entrez KW - CARF domain KW - CRISPR KW - Csx3 KW - archaeoglobus fulgidus KW - biochemistry KW - chemical biology KW - cooperative enzyme KW - cyclic tetra-adenylate JF - eLife JO - Elife VL - 9 N2 - Type III CRISPR systems detect foreign RNA and activate the cyclase domain of the Cas10 subunit, generating cyclic oligoadenylate (cOA) molecules that act as a second messenger to signal infection, activating nucleases that degrade the nucleic acid of both invader and host. This can lead to dormancy or cell death; to avoid this, cells need a way to remove cOA from the cell once a viral infection has been defeated. Enzymes specialised for this task are known as ring nucleases, but are limited in their distribution. Here, we demonstrate that the widespread CRISPR associated protein Csx3, previously described as an RNA deadenylase, is a ring nuclease that rapidly degrades cyclic tetra-adenylate (cA4). The enzyme has an unusual cooperative reaction mechanism involving an active site that spans the interface between two dimers, sandwiching the cA4 substrate. We propose the name Crn3 (CRISPR associated ring nuclease 3) for the Csx3 family. SN - 2050-084X UR - https://www.unboundmedicine.com/medline/citation/32597755/Tetramerisation_of_the_CRISPR_ring_nuclease_Crn3/Csx3_facilitates_cyclic_oligoadenylate_cleavage L2 - https://doi.org/10.7554/eLife.57627 DB - PRIME DP - Unbound Medicine ER -
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