Key result
Cryo-EM analysis of the Cmr-β complex revealed its unique subunit architecture and how target RNA binding induces conformational changes in Cmr2 and Cmr3 to regulate the immune response.
Why the study?
How target RNA binding regulates Cmr2 activities and the multifaceted immune response in the Cmr-β Type III-B CRISPR-Cas complex was not fully understood.
The study reveals the structural basis for how target RNA binding regulates the multifaceted immune response of the Type III-B CRISPR-Cas complex Cmr-β.
Cmr-β is a Type III-B CRISPR-Cas complex that upon target RNA recognition unleashes a multifaceted immune response against invading genetic elements, including ssDNA cleavage, cyclic oligoadenylate synthesis, and also a unique UA-specific ssRNA hydrolysis by the Cmr2 subunit. Here, we present the structure-function relationship of Cmr-β unveiling how binding of the target RNA regulates the Cmr2 activities. CryoEM analysis revealed the unique subunit architecture of Cmr-β and captured the complex in different conformational stages of the immune response, including the non-cognate and cognate target-RNA bound complexes. The binding of the target RNA induces a conformational change of Cmr2, which together with the complementation between the 5’-handle in the crRNA and the 3’-antitag of the target RNA, activate different configurations in a unique loop of the Cmr3 subunit, which acts as an allosteric sensor signaling the self vs. non-self recognition. These findings highlight the diverse defense strategies of Type III complexes.
No takes yet. Share an insight, caveat, or question.
Sofos et al. (2020) studied this question. Cryo-EM analysis of the Cmr-β complex revealed its unique subunit architecture and how target RNA binding induces conformational changes in Cmr2 and Cmr3 to regulate the immune response.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: