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Publication Abstract from PubMed

The CRISPR-Cas type III-E RNA-targeting effector complex gRAMP/Cas7-11 is associated with a caspase-like protein (TPR-CHAT/Csx29) to form Craspase (CRISPR-guided caspase). Here, we use cryo-electron microscopy snapshots of Craspase to explain its target RNA cleavage and protease activation mechanisms. Target-guide pairing extending into the 5' region of the guide RNA displaces a gating loop in gRAMP, which triggers an extensive conformational relay that allosterically aligns the protease catalytic dyad and opens an amino acid side-chain-binding pocket. We further define Csx30 as the endogenous protein substrate that is site-specifically proteolyzed by RNA-activated Craspase. This protease activity is switched off by target RNA cleavage by gRAMP and is not activated by RNA targets containing a matching protospacer flanking sequence. We thus conclude that Craspase is a target RNA-activated protease with self-regulatory capacity.

Craspase is a CRISPR RNA-guided, RNA-activated protease.,Hu C, van Beljouw SPB, Nam KH, Schuler G, Ding F, Cui Y, Rodriguez-Molina A, Haagsma AC, Valk M, Pabst M, Brouns SJJ, Ke A Science. 2022 Sep 16;377(6612):1278-1285. doi: 10.1126/science.add5064. Epub 2022 , Aug 25. PMID:36007061^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.