Structures of the Cmr-β Complex Reveal the Regulation of the Immunity Mechanism of Type III-B CRISPR-Cas

Mol Cell. 2020 Sep 3;79(5):741-757.e7. doi: 10.1016/j.molcel.2020.07.008. Epub 2020 Jul 29.


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 single-stranded DNA (ssDNA) cleavage, cyclic oligoadenylate synthesis, and also a unique UA-specific single-stranded RNA (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. Cryoelectron microscopy (cryo-EM) 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' tag in the CRISPR RNAs (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- versus non-self-recognition. These findings highlight the diverse defense strategies of type III complexes.

Keywords: CRISPR-Cas; cryoEM; genome editing; immunity; molecular biology; protein-nucleic acid interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / physiology*
  • Archaeal Proteins / chemistry
  • Archaeal Proteins / physiology
  • Archaeal Proteins / ultrastructure
  • CRISPR-Associated Proteins / chemistry*
  • CRISPR-Associated Proteins / physiology*
  • CRISPR-Associated Proteins / ultrastructure
  • Clustered Regularly Interspaced Short Palindromic Repeats* / physiology
  • Cryoelectron Microscopy
  • DNA, Single-Stranded / metabolism
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • RNA, Messenger / metabolism
  • Structure-Activity Relationship
  • Sulfolobus / genetics
  • Sulfolobus / physiology


  • Archaeal Proteins
  • CRISPR-Associated Proteins
  • DNA, Single-Stranded
  • RNA, Messenger