The CRISPR-associated adenosine deaminase Cad1 converts ATP to ITP to provide antiviral immunity.

ABSTRACT: Type III CRISPR systems provide immunity against genetic invaders through the production of cyclic oligo-adenylate (cA_n) molecules that activate effector proteins that contain CRISPR-associated Rossman fold (CARF) domains. Here, we characterized the function and structure of an effector in which the CARF domain is fused to an adenosine deaminase domain, CRISPR-associated adenosine deaminase 1 (Cad1). We show that upon binding of cA₄ or cA₆ to its CARF domain, Cad1 converts ATP to ITP, both in vivo and in vitro. Cryoelectron microscopy (cryo-EM) structural studies on full-length Cad1 reveal an hexameric assembly composed of a trimer of dimers, with bound ATP at inter-domain sites required for activity and ATP/ITP within deaminase active sites. Upon synthesis

SUBMITTER: Baca CF 

PROVIDER: S-EPMC11645235 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature