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

• 成果类型: Article
• 署名作者: VanderWal, Arica R.; Park, Jung-Un; Polevoda, Bogdan; Nicosia, Julia K.; Vargas, Adrian M. Molina; Kellogg, Elizabeth H.; O'Connell, Mitchell R.
• 署名单位: University of Rochester; University of Rochester; Cornell University; University of Rochester; University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9874
• DOI: 10.1126/science.abm1184
• 发表日期: 2023-04-28
• 页码: 410-415
• 关键词: search

摘要

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.