Structures of an active type III-A CRISPR effector complex.

Clustered regularly interspaced short palindromic repeats (CRISPR) and their CRISPR-associated proteins (Cas) provide many prokaryotes with an adaptive immune system against invading genetic material. Type III CRISPR systems are unique in that they can degrade both RNA and DNA. In response to invading nucleic acids, they produce cyclic oligoadenylates that act as secondary messengers, activating cellular nucleases that aid in the immune response. Here, we present seven single-particle cryo-EM structures of the type III-A Staphylococcus epidermidis CRISPR effector complex. The structures reveal the intact S. epidermidis effector complex in an apo, ATP-bound, cognate target RNA-bound, and non-cognate target RNA-bound states and illustrate how the effector complex binds and presents crRNA. The complexes bound to target RNA capture the type III-A effector complex in a post-RNA cleavage state. The ATP-bound structures give details about how ATP binds to Cas10 to facilitate cyclic oligoadenylate production. [Display omitted] • Structures of the S. epidermidis CRISPR effector complex show overall architecture • Structures with either self or non-self target RNA illustrate target recognition • ATP-bound structures show residues involved in cyclic oligoadenylate production • Comparison with previously known structures detail pre- and post-cleavage states Smith et al. present cryo-EM structures of intact and catalytically active S. epidermidis type III-A CRISPR effector complexes in apo, ATP-bound, and self and non-self target RNA-bound states. The structures provide information on the complex overall architecture and stoichiometry, target RNA recognition, and cyclic oligoadenylate production by Cas10. [ABSTRACT FROM AUTHOR]