Type III-B CRISPR-Cas signaling-based cascade of proteolytic cleavages

ABSTRACT: Characteristic for type III CRISPR-Cas systems is the generation of cyclic oligoadenylate (cOA) molecules, which allosterically activate proteins carrying cognate sensory domains: CARF or SAVED. Here, we characterize a type III-B system associated set of genes from Haliangium ochraceum, containing two CBASS co-opted caspase-like proteases, SAVED-CHAT and PCaspase (Prokaryotic Caspase). Cyclic tri-AMP (cA3)- induced oligomerization of the SAVED domains of SAVED-CHAT leads to proteolytic activity of the CHAT domains which, when active, specifically cleave and activate PCaspase. In turn, activated PCaspase cleaves a multitude of proteins and leads to a strong defence mechanism in vivo in E. coli.. Together, our findings show a cascade of proteolytic activities (with conceptual similarities to eukaryotic caspases) and constitute an effective strategy to defend against mobile genetic elements.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Haliangium Ochraceum Dsm 14365

SUBMITTER: Richard Scheltema  

LAB HEAD: Richard Scheltema

PROVIDER: PXD046897 | Pride | 2025-05-06

REPOSITORIES: Pride