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-Structure paper
Title | Csx28 is a membrane pore that enhances CRISPR-Cas13b-dependent antiphage defense. |
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Journal, issue, pages | Science, Vol. 380, Issue 6643, Page 410-415, Year 2023 |
Publish date | Apr 28, 2023 |
Authors | Arica R VanderWal / Jung-Un Park / Bogdan Polevoda / Julia K Nicosia / Adrian M Molina Vargas / Elizabeth H Kellogg / Mitchell R O'Connell / |
PubMed Abstract | 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- ...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. |
External links | Science / PubMed:37104586 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.65 Å |
Structure data | EMDB-40059, PDB-8gi1: |
Source |
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Keywords | ANTIVIRAL PROTEIN / CRISPR-associated protein |