Structural principles of CRISPR-Cas enzymes used in nucleic acid detection

• Published in: Journal of structural biology Vol. 214; no. 1; p. 107838
• Main Authors: Das, Anuska, Goswami, Hemant N., Whyms, Charlisa T., Sridhara, Sagar, Li, Hong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2022
• Subjects: Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Card1; Cas12; Cas13; Cmr; CRISPR-Cas enzyme structures; Csm; Csm6; Csx1; Nucleic acid detection; CRISPR-Cas enzyme structures; Cmr; Csm6; Csx1; Cas13; Cas12; Csm; Card1; Nucleic acid detection
• ISSN: 1047-8477; 1095-8657; 1095-8657
• DOI: 10.1016/j.jsb.2022.107838

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•Three types CRISPR-Cas systems including the associated ancillary enzymes are used in nucleic acid detections.•Molecular mechanisms of these CRISPR-Cas systems are summarized graphically.•Cognate DNA induces domain rearrangement and formation of the RuvC catalytic site in Cas12.•Cognate RNA induces domain rearrangement and formation of a composite HEPN RNA cleavage site in Cas13.•Cognate RNA induces loop rearrangement and possible dynamic changes in the active sites of the Type III systems.•Cyclic oligoadenylates may induce oligomerization or reshaping of the ancillary enzymes.
Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-based technology has revolutionized the field of biomedicine with broad applications in genome editing, therapeutics and diagnostics. While a majority of applications involve the RNA-guided site-specific DNA or RNA cleavage by CRISPR enzymes, recent successes in nucleic acid detection rely on their collateral and non-specific cleavage activated by viral DNA or RNA. Ranging in enzyme composition, the mechanism for distinguishing self- from foreign-nucleic acids, the usage of second messengers, and enzymology, the CRISPR enzymes provide a diverse set of diagnosis tools in further innovations. Structural biology plays an important role in elucidating the mechanisms of these CRISPR enzymes. Here we summarize and compare structures of three types of CRISPR enzymes used in nucleic acid detection captured in their respective functional forms and illustrate the current understanding of their activation mechanism.