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TitleDdmDE eliminates plasmid invasion by DNA-guided DNA targeting.
Journal, issue, pagesCell, Vol. 187, Issue 19, Page 5253-5266.e16, Year 2024
Publish dateSep 19, 2024
AuthorsXiao-Yuan Yang / Zhangfei Shen / Chen Wang / Kotaro Nakanishi / Tian-Min Fu /
PubMed AbstractHorizontal 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 ...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.
External linksCell / PubMed:39173632 / PubMed Central
MethodsEM (single particle)
Resolution3.07 - 3.56 Å
Structure data

44486

9bf1

EMDB-44486, PDB-9bf1:
Structure of apo-state V. cholerae DdmD
Method: EM (single particle) / Resolution: 3.1 Å

44490

9bf5

EMDB-44490, PDB-9bf5:
Structure of V. cholerae DdmD in complex with ssDNA
Method: EM (single particle) / Resolution: 3.07 Å

EMDB-44515: Constituent EM map for the consensus map of DdmDE complex
Method: EM (single particle) / Resolution: 3.34 Å

44516

9bgk

EMDB-44516, PDB-9bgk:
Structure of V.cholera DdmDE (2D:1E) in complex with DNA
Method: EM (single particle) / Resolution: 3.28 Å

EMDB-44562: Cryo-EM density map of DdmDE(1:1) complex bound with DNA
Method: EM (single particle) / Resolution: 3.56 Å

EMDB-44563: Cryo-EM map of DdmDE(1:1) complex bound with DNA
Method: EM (single particle) / Resolution: 3.32 Å

45254

9c6q

EMDB-45254, PDB-9c6q:
Structure of V. cholerae monomeric DdmD bound with ssDNA
Method: EM (single particle) / Resolution: 3.18 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • vibrio cholerae (bacteria)
KeywordsIMMUNE SYSTEM / Vibrio cholerae / bacteria / anti-plasmids / defense system / DNA defense modules(Ddm) / DdmDE / IMMUNE SYSTEM/DNA / anti-plasmid / IMMUNE SYSTEM-DNA complex / DNA defense modules (Ddm) / bacterial immune system

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