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-Structure paper
タイトル | Plasmid targeting and destruction by the DdmDE bacterial defence system. |
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ジャーナル・号・ページ | Nature, Vol. 630, Issue 8018, Page 961-967, Year 2024 |
掲載日 | 2024年5月13日 |
著者 | Jack P K Bravo / Delisa A Ramos / Rodrigo Fregoso Ocampo / Caiden Ingram / David W Taylor / |
PubMed 要旨 | Although eukaryotic Argonautes have a pivotal role in post-transcriptional gene regulation through nucleic acid cleavage, some short prokaryotic Argonaute variants (pAgos) rely on auxiliary nuclease ...Although eukaryotic Argonautes have a pivotal role in post-transcriptional gene regulation through nucleic acid cleavage, some short prokaryotic Argonaute variants (pAgos) rely on auxiliary nuclease factors for efficient foreign DNA degradation. Here we reveal the activation pathway of the DNA defence module DdmDE system, which rapidly eliminates small, multicopy plasmids from the Vibrio cholerae seventh pandemic strain (7PET). Through a combination of cryo-electron microscopy, biochemistry and in vivo plasmid clearance assays, we demonstrate that DdmE is a catalytically inactive, DNA-guided, DNA-targeting pAgo with a distinctive insertion domain. We observe that the helicase-nuclease DdmD transitions from an autoinhibited, dimeric complex to a monomeric state upon loading of single-stranded DNA targets. Furthermore, the complete structure of the DdmDE-guide-target handover complex provides a comprehensive view into how DNA recognition triggers processive plasmid destruction. Our work establishes a mechanistic foundation for how pAgos utilize ancillary factors to achieve plasmid clearance, and provides insights into anti-plasmid immunity in bacteria. |
リンク | Nature / PubMed:38740055 |
手法 | EM (単粒子) |
解像度 | 2.5 - 3.2 Å |
構造データ | EMDB-41781, PDB-8u0j: EMDB-41785, PDB-8u0u: EMDB-41790, PDB-8u0w: EMDB-41865, PDB-8u3k: EMDB-44825: DdmD dimer apoprotein (CASP target) |
化合物 | ChemComp-MG: |
由来 |
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キーワード | IMMUNE SYSTEM/DNA / DdmE / Argonaute / pAgo / IMMUNE SYSTEM / IMMUNE SYSTEM-DNA complex / DdmD / helicase / nuclease |