Target RNA activates the protease activity of Craspase to confer antiviral defense.
Mol Cell
; 82(23): 4503-4518.e8, 2022 12 01.
Article
in En
| MEDLINE
| ID: mdl-36306795
ABSTRACT
In the type III-E CRISPR-Cas system, a Cas effector (gRAMP) is associated with a TPR-CHAT to form Craspase (CRISPR-guided caspase). However, both the structural features of gRAMP and the immunity mechanism remain unknown for this system. Here, we report structures of gRAMP-crRNA and gRAMPcRNAtarget RNA as well as structures of Craspase and Craspase complexed with cognate target RNA (CTR) or non-cognate target RNA (NTR). Importantly, the 3' anti-tag region of NTR and CTR binds at two distinct channels in Craspase, and CTR with a non-complementary 3' anti-tag induces a marked conformational change of the TPR-CHAT, which allosterically activates its protease activity to cleave an ancillary protein Csx30. This cleavage then triggers an abortive infection as the antiviral strategy of the type III-E system. Together, our study provides crucial insights into both the catalytic mechanism of the gRAMP and the immunity mechanism of the type III-E system.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CRISPR-Associated Proteins
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2022
Type:
Article
Affiliation country:
China