Craspase is a CRISPR RNA-guided, RNA-activated protease.

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  • Additional Information
    • Source:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE
    • Publication Information:
      Publication: : Washington, DC : American Association for the Advancement of Science
      Original Publication: New York, N.Y. : [s.n.] 1880-
    • Subject Terms:
      Bacterial Proteins*/chemistry ; CRISPR-Associated Proteins*/chemistry ; CRISPR-Cas Systems* ; Caspases*/chemistry ; Planctomycetes*/enzymology ; RNA, Guide, CRISPR-Cas Systems*/chemistry; Cryoelectron Microscopy ; Protein Conformation
    • Abstract:
      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.
    • Comments:
      Comment in: Funct Integr Genomics. 2023 Mar 23;23(2):98. doi: 10.1007/s10142-023-01024-0. (PMID: 36952053)
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    • Grant Information:
      R35 GM118174 United States GM NIGMS NIH HHS
    • Accession Number:
      0 (Bacterial Proteins)
      0 (CRISPR-Associated Proteins)
      0 (RNA, Guide, CRISPR-Cas Systems)
      EC 3.4.22.- (Caspases)
    • Publication Date:
      Date Created: 20220825 Date Completed: 20220919 Latest Revision: 20240104
    • Publication Date:
      20250114
    • Accession Number:
      PMC10041820
    • Accession Number:
      10.1126/science.add5064
    • Accession Number:
      36007061