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Cryo-EM structure of the type Ⅲ-E CRISPR-Cas effector gRAMP in complex with TPR-CHAT

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Dear Editor, Prokaryotes and viruses have been engaged in an evolutionary struggle for billions of years.1 Bacteria and archaea employ clustered regularly interspaced short palindromic repeats(CRISPR)-CRISPR-associated(Cas)adaptive immune systems to protect against viral infection.2 The CRISPR-Cas locus consists of two parts:CRISPR and Cas genes.According to the latest phylogenetic classification,the CRISPR-Cas system can be divided into two classes,which can be further subdivided into six types.3 Class 1 CRISPR-Cas systems are characterized by a multiprotein effector,and consist of type Ⅰ,Ⅲ,and Ⅳ CRISPR-Cas systems.Class 2 CRISPR-Cas systems feature a single nuclease protein,and consist of type Ⅱ,Ⅴ,and Ⅵ CRISPR-Cas systems.The type Ⅱ Cas9 and type Ⅴ Cas12 systems have been engineered as genome editing tools,and they have been successfully applied in a broad range of organisms.4,5 Compared to Cas9,the type ⅥCas13 system exhibits RNA-guided RNase activity and the property of nonspecific cutting.6 Recently,a new subtype of CRISPR-Cas,type Ⅲ-E,3 has been identified and named gRAMP7 or Cas7-11.8 Unlike the traditional effectors of the type Ⅲ CRISPR-Cas system,gRAMP is a single effector protein with four Cas7 proteins and one Cas11 protein fused together.Given its unique architecture and specific cleavage activity,gRAMP is expected to be engineered as a powerful RNA editing tool.8 Interestingly,a gene encoding the caspase-like peptidase TPR-CHAT often co-occurs with gRAMP gene clusters.3 TPR-CHAT interacts directly with gRAMP,7 indicat-ing a functional relationship between the CRISPR-Cas system and caspase peptidase.However,the exact mechanism of the recognition and cleavage of target ssRNA by gRAMP from Candidatus"Scalindua brodae"(Sb-gRAMP),7 as well as the molecular architecture of the CRISPR-guided caspase complex,remain unclear.

crispr-cas、structure、with、complex、cryo-em、effector、gramp、tpr-chat、type

32

Q78;R378;O

2023-02-10(万方平台首次上网日期,不代表论文的发表时间)

共4页

1128-1131

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细胞研究(英文版)

1001-0602

31-1568

32

2022,32(12)

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