9BGK

Structure of V.cholera DdmDE (2D:1E) in complex with DNA

Summary for 9BGK

• Entry DOI: 10.2210/pdb9bgk/pdb
• EMDB information: 44516
• Descriptor: guide DNA, complementary target DNA, non-complementary target DNA (long), ... (7 entities in total)
• Functional Keywords: dna defense modules (ddm), ddmde, anti-plasmid, bacterial immune system, immune system-dna complex, immune system/dna
• Biological source: Vibrio cholerae; More
• Total number of polymer chains: 7
• Total formula weight: 374688.86

Authors

Shen, Z.F.,Yang, X.Y.,Fu, T.M. (deposition date: 2024-04-19, release date: 2024-10-23, Last modification date: 2024-11-06)

Primary citation

Yang, X.Y.,Shen, Z.,Wang, C.,Nakanishi, K.,Fu, T.M.
DdmDE eliminates plasmid invasion by DNA-guided DNA targeting.
Cell, 187:5253-5266.e16, 2024

PubMed Abstract: Horizontal gene transfer is a key driver of bacterial evolution, but it also presents severe risks to bacteria by introducing invasive mobile genetic elements. To counter these threats, bacteria have developed various defense systems, including prokaryotic Argonautes (pAgos) and the DNA defense module DdmDE system. Through biochemical analysis, structural determination, and in vivo plasmid clearance assays, we elucidate the assembly and activation mechanisms of DdmDE, which eliminates small, multicopy plasmids. We demonstrate that DdmE, a pAgo-like protein, acts as a catalytically inactive, DNA-guided, DNA-targeting defense module. In the presence of guide DNA, DdmE targets plasmids and recruits a dimeric DdmD, which contains nuclease and helicase domains. Upon binding to DNA substrates, DdmD transitions from an autoinhibited dimer to an active monomer, which then translocates along and cleaves the plasmids. Together, our findings reveal the intricate mechanisms underlying DdmDE-mediated plasmid clearance, offering fundamental insights into bacterial defense systems against plasmid invasions.

PubMed: 39173632
DOI: 10.1016/j.cell.2024.07.028

Experimental method

ELECTRON MICROSCOPY (3.28 Å)