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8wm4

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

Structural highlights

8wm4 is a 2 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 2.93Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A401FT36_9BACT

Publication Abstract from PubMed

CRISPRâCas7-11 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 CRISPRâCas7-11 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^[1]

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

References

↑ 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. Structural basis of negative regulation of CRISPR-Cas7-11 by TPR-CHAT. Signal Transduct Target Ther. 2024 May 13;9(1):111. PMID:38735995 doi:10.1038/s41392-024-01821-4