8wmc

Cryo-EM structure of DiCas7-11-crRNA in complex with regulator

spinqualitylabelsall models 8wmc, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8wmc is a 3 chain structure with sequence from Desulfonema ishimotonii and Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.9Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A401FT52_9BACT Publication Abstract from PubMed CRISPR‒Cas7-11 is a Type III-E CRISPR-associated nuclease that functions as a potent RNA editing tool. Tetratrico-peptide repeat fused with Cas/HEF1-associated signal transducer (TPR-CHAT) acts as a regulatory protein that interacts with CRISPR RNA (crRNA)-bound Cas7-11 to form a CRISPR-guided caspase complex (Craspase). However, the precise modulation of Cas7-11's nuclease activity by TPR-CHAT to enhance its utility requires further study. Here, we report cryo-electron microscopy (cryo-EM) structures of Desulfonema ishimotonii (Di) Cas7-11-crRNA, complexed with or without the full length or the N-terminus of TPR-CHAT. These structures unveil the molecular features of the Craspase complex. Structural analysis, combined with in vitro nuclease assay and electrophoretic mobility shift assay, reveals that DiTPR-CHAT negatively regulates the activity of DiCas7-11 by preventing target RNA from binding through the N-terminal 65 amino acids of DiTPR-CHAT (DiTPR-CHAT(NTD)). Our work demonstrates that DiTPR-CHAT(NTD) can function as a small unit of DiCas7-11 regulator, potentially enabling safe applications to prevent overcutting and off-target effects of the CRISPR‒Cas7-11 system. Structural basis of negative regulation of CRISPR-Cas7-11 by TPR-CHAT.,Hong T, Luo Q, Ma H, Wang X, Li X, Shen C, Pang J, Wang Y, Chen Y, Zhang C, Su Z, Dong H, Tang X Signal Transduct Target Ther. 2024 May 13;9(1):111. doi: , 10.1038/s41392-024-01821-4. PMID:38735995 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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