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-Structure paper
タイトル | RNA-activated protein cleavage with a CRISPR-associated endopeptidase. |
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ジャーナル・号・ページ | Science, Vol. 378, Issue 6622, Page 874-881, Year 2022 |
掲載日 | 2022年11月25日 |
著者 | Jonathan Strecker / F Esra Demircioglu / David Li / Guilhem Faure / Max E Wilkinson / Jonathan S Gootenberg / Omar O Abudayyeh / Hiroshi Nishimasu / Rhiannon K Macrae / Feng Zhang / |
PubMed 要旨 | In prokaryotes, CRISPR-Cas systems provide adaptive immune responses against foreign genetic elements through RNA-guided nuclease activity. Recently, additional genes with non-nuclease functions have ...In prokaryotes, CRISPR-Cas systems provide adaptive immune responses against foreign genetic elements through RNA-guided nuclease activity. Recently, additional genes with non-nuclease functions have been found in genetic association with CRISPR systems, suggesting that there may be other RNA-guided non-nucleolytic enzymes. One such gene from encodes the TPR-CHAT protease Csx29, which is associated with the CRISPR effector Cas7-11. Here, we demonstrate that this CRISPR-associated protease (CASP) exhibits programmable RNA-activated endopeptidase activity against a sigma factor inhibitor to regulate a transcriptional response. Cryo-electron microscopy of an active and substrate-bound CASP complex reveals an allosteric activation mechanism that reorganizes Csx29 catalytic residues upon target RNA binding. This work reveals an RNA-guided function in nature that can be leveraged for RNA-sensing applications in vitro and in human cells. |
リンク | Science / PubMed:36423276 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.53 - 3.15 Å |
構造データ | EMDB-28064: Cas7-11 in complex with Csx29, focus refined on Cas7-11 EMDB-28065, PDB-8eey: EMDB-28070: Cas7-11 in complex with Csx29, focus refined on Csx29 EMDB-28071: Cas7-11 in complex with DR-mismatched target RNA, Csx29 and Csx30, focus refined on Cas7-11 INS domain EMDB-28072: Cas7-11 in complex with DR-mismatched target RNA, Csx29 and Csx30, focus refined on Csx29 EMDB-28073: Cas7-11 in complex with DR-mismatched target RNA, Csx29 and Csx30, focus refined on Csx29 CHAT domain and Csx30 |
化合物 | ChemComp-ZN: |
由来 |
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キーワード | RNA BINDING PROTEIN/RNA / CRISPR / endonuclease / endopeptidase / RNA BINDING PROTEIN-RNA complex |