Antiviral type III CRISPR signalling via conjugation of ATP and SAM.

Autor: Chi H; Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK., Hoikkala V; Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK.; University of Jyväskylä, Department of Biological and Environmental Science and Nanoscience Center, Jyväskylä, Finland., Grüschow S; Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK., Graham S; Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK., Shirran S; Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK., White MF; Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK. mfw2@st-andrews.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2023 Oct; Vol. 622 (7984), pp. 826-833. Date of Electronic Publication: 2023 Oct 18.
DOI: 10.1038/s41586-023-06620-5
Abstrakt: CRISPR systems are widespread in the prokaryotic world, providing adaptive immunity against mobile genetic elements 1,2 . Type III CRISPR systems, with the signature gene cas10, use CRISPR RNA to detect non-self RNA, activating the enzymatic Cas10 subunit to defend the cell against mobile genetic elements either directly, via the integral histidine-aspartate (HD) nuclease domain 3-5 or indirectly, via synthesis of cyclic oligoadenylate second messengers to activate diverse ancillary effectors 6-9 . A subset of type III CRISPR systems encode an uncharacterized CorA-family membrane protein and an associated NrN family phosphodiesterase that are predicted to function in antiviral defence. Here we demonstrate that the CorA-associated type III-B (Cmr) CRISPR system from Bacteroides fragilis provides immunity against mobile genetic elements when expressed in Escherichia coli. However, B. fragilis Cmr does not synthesize cyclic oligoadenylate species on activation, instead generating S-adenosyl methionine (SAM)-AMP (SAM is also known as AdoMet) by conjugating ATP to SAM via a phosphodiester bond. Once synthesized, SAM-AMP binds to the CorA effector, presumably leading to cell dormancy or death by disruption of the membrane integrity. SAM-AMP is degraded by CRISPR-associated phosphodiesterases or a SAM-AMP lyase, potentially providing an 'off switch' analogous to cyclic oligoadenylate-specific ring nucleases 10 . SAM-AMP thus represents a new class of second messenger for antiviral signalling, which may function in different roles in diverse cellular contexts.
(© 2023. The Author(s).)
Databáze: MEDLINE
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