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-Structure paper
| タイトル | Molecular basis for dual-spacer-guided target cleavage by the TIGR-TasH system. |
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| ジャーナル・号・ページ | Mol Cell, Vol. 86, Issue 7, Page 1217-11229.e6, Year 2026 |
| 掲載日 | 2026年4月2日 |
著者 | Jie Yang / Tongyao Wang / Zhikun Liu / Wenqi Wu / Yangyue Sun / Yancheng Zhan / Shuqin Zhang / Hong Chen / Bin Liu / Caidie Yue / Zhenning Yin / Zhengda Shan / Xuzichao Li / Zhuang Li / Zhiyong Yuan / Hang Yin / Heng Zhang / ![]() |
| PubMed 要旨 | The RNA-directed programmable nuclease systems, exemplified by the CRISPR-Cas system, have been widely used in genome editing. In contrast to the single-spacer configuration of CRISPR RNA (crRNA), ...The RNA-directed programmable nuclease systems, exemplified by the CRISPR-Cas system, have been widely used in genome editing. In contrast to the single-spacer configuration of CRISPR RNA (crRNA), the guide RNA (tigRNA) of the tandem interspaced guide RNA (TIGR) system features a dual-spacer arrangement, thereby directing the TIGR-associated (Tas) protein to engage both strands of the target double-stranded DNA (dsDNA). Here, we determine six cryo-electron microscopy structures of the Salicola phage TIGR-TasH complex. The central coiled-coil region of TasH mediates dimerization, while the C-terminal nucleolar protein (Nop) domain is able to autonomously process precursor tigRNA. Upon target binding, the dynamic N-terminal HNH nuclease domain is recruited for cleavage through a β-hairpin, which also determines the target preference. More interestingly, the conserved box C motif of tigRNA stabilizes this β-hairpin in an adenine-specific manner, enabling us to rationally design a guide RNA-defined nickase, distinct from conventional protein-based nickase strategies used in genome editing. |
リンク | Mol Cell / PubMed:41831437 |
| 手法 | EM (単粒子) |
| 解像度 | 2.33 - 3.3 Å |
| 構造データ | EMDB-65487, PDB-9vzx: EMDB-65489, PDB-9w02: EMDB-65490, PDB-9w03: EMDB-65491, PDB-9w04: EMDB-65567, PDB-9w26: EMDB-67763, PDB-21kl: |
| 化合物 | ![]() ChemComp-MG: |
| 由来 |
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キーワード | ANTIVAL PROTEIN/RNA/DNA / protein complex / ANTIVIRAL PROTEIN/RNA/DNA / ANTIVAL PROTEIN-RNA-DNA complex / ANTIVIRAL PROTEIN |
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salicola phage cgphi29 (ファージ)
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