Type III-B CRISPR-Cas cascade of proteolytic cleavages

• 成果类型: Article
• 署名作者: Steens, Jurre A.; Bravo, Jack P. K.; Salazar, Carl Raymund P.; Yildiz, Caglar; Amieiro, Afonso M.; Kostlbacher, Stephan; Prinsen, Stijn H. P.; Andres, Ane S.; Patinios, Constantinos; Bardis, Andreas; Barendregt, Arjan; Scheltema, Richard A.; Ettema, Thijs J. G.; van der Oost, John; Taylor, David W.; Staals, Raymond H. J.
• 署名单位: Wageningen University & Research; University of Texas System; University of Texas Austin; Utrecht University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11233
• DOI: 10.1126/science.adk0378
• 发表日期: 2024-02-02
• 页码: 512-519
• 关键词: caspase family; dna cleavage; metacaspases; mechanism; proteases; effector; phage

摘要

The generation of cyclic oligoadenylates and subsequent allosteric activation of proteins that carry sensory domains is a distinctive feature of type III CRISPR-Cas systems. In this work, we characterize a set of associated genes of a type III-B system from Haliangium ochraceum that contains two caspase-like proteases, SAVED-CHAT and PCaspase (prokaryotic caspase), co-opted from a cyclic oligonucleotide-based antiphage signaling system (CBASS). Cyclic tri-adenosine monophosphate (AMP)-induced oligomerization of SAVED-CHAT activates proteolytic activity of the CHAT domains, which specifically cleave and activate PCaspase. Subsequently, activated PCaspase cleaves a multitude of proteins, which results in a strong interference phenotype in vivo in Escherichia coli. Taken together, our findings reveal how a CRISPR-Cas-based detection of a target RNA triggers a cascade of caspase-associated proteolytic activities.