The CRISPR ancillary effector Can2 is a dual-specificity nuclease potentiating type III CRISPR defence.
CRISPR-Associated Proteins
/ chemistry
CRISPR-Cas Systems
Clostridiales
/ enzymology
Clustered Regularly Interspaced Short Palindromic Repeats
DNA
/ chemistry
Deoxyribonuclease I
/ chemistry
Enzyme Activation
Escherichia coli
/ virology
Interspersed Repetitive Sequences
Metals
/ chemistry
Models, Molecular
Protein Domains
Ribonucleases
/ chemistry
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 03 2021
18 03 2021
Historique:
accepted:
27
01
2021
revised:
22
01
2021
received:
22
12
2020
pubmed:
17
2
2021
medline:
27
3
2021
entrez:
16
2
2021
Statut:
ppublish
Résumé
Cells and organisms have a wide range of mechanisms to defend against infection by viruses and other mobile genetic elements (MGE). Type III CRISPR systems detect foreign RNA and typically generate cyclic oligoadenylate (cOA) second messengers that bind to ancillary proteins with CARF (CRISPR associated Rossman fold) domains. This results in the activation of fused effector domains for antiviral defence. The best characterised CARF family effectors are the Csm6/Csx1 ribonucleases and DNA nickase Can1. Here we investigate a widely distributed CARF family effector with a nuclease domain, which we name Can2 (CRISPR ancillary nuclease 2). Can2 is activated by cyclic tetra-adenylate (cA4) and displays both DNase and RNase activity, providing effective immunity against plasmid transformation and bacteriophage infection in Escherichia coli. The structure of Can2 in complex with cA4 suggests a mechanism for the cA4-mediated activation of the enzyme, whereby an active site cleft is exposed on binding the activator. These findings extend our understanding of type III CRISPR cOA signalling and effector function.
Identifiants
pubmed: 33590098
pii: 6137369
doi: 10.1093/nar/gkab073
pmc: PMC7969007
doi:
Substances chimiques
CRISPR-Associated Proteins
0
Metals
0
DNA
9007-49-2
Ribonucleases
EC 3.1.-
Deoxyribonuclease I
EC 3.1.21.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2777-2789Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S000313/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T004789/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204821/Z/16/Z
Pays : United Kingdom
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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