8U0J

DdmE in complex with guide and target DNA

Summary for 8U0J

• Entry DOI: 10.2210/pdb8u0j/pdb
• EMDB information: 41781
• Descriptor: DdmE, DNA (5'-D(P*GP*TP*TP*AP*GP*AP*CP*TP*TP*TP*AP*AP*GP*T)-3'), DNA (5'-D(P*AP*CP*TP*TP*AP*AP*AP*GP*TP*CP*TP*AP*AP*CP*CP*TP*AP*TP*AP*GP*GP*AP*T)-3'), ... (5 entities in total)
• Functional Keywords: ddme, argonaute, pago, immune system, immune system-dna complex, immune system/dna
• Biological source: Vibrio cholerae; More
• Total number of polymer chains: 4
• Total formula weight: 92864.62

Authors

Bravo, J.P.K. (deposition date: 2023-08-29, release date: 2024-07-03, Last modification date: 2024-07-10)

Primary citation

Bravo, J.P.K.,Ramos, D.A.,Fregoso Ocampo, R.,Ingram, C.,Taylor, D.W.
Plasmid targeting and destruction by the DdmDE bacterial defence system.
Nature, 630:961-967, 2024

PubMed Abstract: 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.

PubMed: 38740055
DOI: 10.1038/s41586-024-07515-9

Experimental method

ELECTRON MICROSCOPY (3.1 Å)