Cap1 forms a cyclic tetra-adenylate-induced membrane pore during the type III-A CRISPR-Cas immune response.

ABSTRACT: During type III CRISPR-Cas immunity in prokaryotes, RNA-guided recognition of viral (phage) transcripts stimulates the Cas10 complex to convert ATP into cyclic oligoadenylates. These act as signaling molecules that bind to CARF proteins and activate their effector domains. Here, we report the structure and function of the Cap1 effector, composed of a pair of transmembrane helices (TM1/2), a CARF-like (CARFL) domain and a domain of unknown function (DUF4579). Cryo-EM studies on apo- and ligand-bound states of Cap1 in glyco-diosgenin detergent revealed the formation of tetrameric complexes in both states, with one cyclic tetra-adenylate molecule bound in a pocket composed by the four CARFL domains. Binding of cA₄ triggers conformational changes that widen an otherwise narrow pore

SUBMITTER: Majumder P 

PROVIDER: S-EPMC12642688 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature