Upon activation by cyclic tetra-adenylate, Cami1 cleaves mRNA exposed at the ribosomal A-site, leading to cell growth arrest through a mechanism paralleling eukaryotic ribosome-inactivating proteins.
The study reveals the structural mechanism by which the CRISPR-associated Cami1 protein inhibits translation upon activation by cyclic oligoadenylate signaling.
Prokaryotic type III CRISPR-Cas antiviral systems employ cyclic oligoadenylate (cA n ) signaling to activate a diverse range of auxiliary proteins that reinforce the CRISPR-Cas defense. Here we characterize a class of cA n -dependent effector proteins named CRISPR-Cas-associated messenger RNA (mRNA) interferase 1 (Cami1) consisting of a CRISPR-associated Rossmann fold sensor domain fused to winged helix-turn-helix and a RelE-family mRNA interferase domain. Upon activation by cyclic tetra-adenylate (cA 4 ), Cami1 cleaves mRNA exposed at the ribosomal A-site thereby depleting mRNA and leading to cell growth arrest. The structures of apo-Cami1 and the ribosome-bound Cami1-cA 4 complex delineate the conformational changes that lead to Cami1 activation and the mechanism of Cami1 binding to a bacterial ribosome, revealing unexpected parallels with eukaryotic ribosome-inactivating proteins.
Mogila et al. (Thu,) reported a other. Cami1 (CRISPR-Cas-associated mRNA interferase 1) was evaluated on Mechanism of Cami1 activation and binding to bacterial ribosome. Upon activation by cyclic tetra-adenylate, Cami1 cleaves mRNA exposed at the ribosomal A-site, leading to cell growth arrest through a mechanism paralleling eukaryotic ribosome-inactivating proteins.