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Structural basis of negative regulation of CRISPR-Cas7-11 by TPR-CHAT.
Hong, Tian; Luo, Qinghua; Ma, Haiyun; Wang, Xin; Li, Xinqiong; Shen, Chongrong; Pang, Jie; Wang, Yan; Chen, Yuejia; Zhang, Changbin; Su, Zhaoming; Dong, Haohao; Tang, Xiaodi.
Afiliación
  • Hong T; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • Luo Q; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • Ma H; Frontiers Medical Center, Tianfu Jincheng Laboratory, West China Hospital, Sichuan University, Chengdu, China.
  • Wang X; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • Li X; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • Shen C; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • Pang J; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • Wang Y; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • Chen Y; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • Zhang C; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • Su Z; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • Dong H; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China. zsu@scu.edu.cn.
  • Tang X; Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China. haohaodong@scu.edu.cn.
Signal Transduct Target Ther ; 9(1): 111, 2024 May 13.
Article en En | MEDLINE | ID: mdl-38735995
ABSTRACT
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-CHATNTD). Our work demonstrates that DiTPR-CHATNTD 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microscopía por Crioelectrón / Proteínas Asociadas a CRISPR / Sistemas CRISPR-Cas Idioma: En Revista: Signal Transduct Target Ther Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microscopía por Crioelectrón / Proteínas Asociadas a CRISPR / Sistemas CRISPR-Cas Idioma: En Revista: Signal Transduct Target Ther Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido