Csx28 is a membrane pore that enhances CRISPR-Cas13b-dependent antiphage defense

Type VI CRISPR-Cas systems use RNA-guided ribonuclease (RNase) Cas13 to defend bacteria against viruses, and some of these systems encode putative membrane proteins that have unclear roles in Cas13-mediated defense. We show that Csx28, of type VI-B2 systems, is a transmembrane protein that assists t...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2023-04, Vol.380 (6643), p.410-415
Main Authors: VanderWal, Arica R, Park, Jung-Un, Polevoda, Bogdan, Nicosia, Julia K, Molina Vargas, Adrian M, Kellogg, Elizabeth H, O'Connell, Mitchell R
Format: Article
Language:English
Subjects:
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Bacteriophage lambda - metabolism
Bacteriophages - metabolism
CRISPR
CRISPR-Associated Proteins - chemistry
CRISPR-Associated Proteins - metabolism
CRISPR-Cas Systems
Cryoelectron Microscopy
Electron microscopy
Endodeoxyribonucleases - chemistry
Endodeoxyribonucleases - metabolism
Escherichia coli - enzymology
Escherichia coli - virology
Membrane Proteins - metabolism
Membranes
Nuclease
Prevotella - enzymology
Prevotella - virology
Proteins
RNA Cleavage
RNA, Viral - metabolism
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Summary:Type VI CRISPR-Cas systems use RNA-guided ribonuclease (RNase) Cas13 to defend bacteria against viruses, and some of these systems encode putative membrane proteins that have unclear roles in Cas13-mediated defense. We show that Csx28, of type VI-B2 systems, is a transmembrane protein that assists to slow cellular metabolism upon viral infection, increasing antiviral defense. High-resolution cryo-electron microscopy reveals that Csx28 forms an octameric pore-like structure. These Csx28 pores localize to the inner membrane in vivo. Csx28's antiviral activity in vivo requires sequence-specific cleavage of viral messenger RNAs by Cas13b, which subsequently results in membrane depolarization, slowed metabolism, and inhibition of sustained viral infection. Our work suggests a mechanism by which Csx28 acts as a downstream, Cas13b-dependent effector protein that uses membrane perturbation as an antiviral defense strategy.
ISSN:0036-8075
1095-9203
1095-9203
DOI:10.1126/science.abm1184