Molecular mechanism of plasmid elimination by the DdmDE defense system

• 成果类型: Article
• 署名作者: Loeff, Luuk; Adams, David W.; Chanez, Christelle; Stutzmann, Sandrine; Righi, Laurie; Blokesch, Melanie; Jinek, Martin
• 署名单位: University of Zurich; Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11815
• DOI: 10.1126/science.adq0534
• 发表日期: 2024-07-12
• 页码: 188-194
• 关键词: antiviral defense; protect bacteria; immune-system; cryo-em; dna; sequence; degradation; alignment; cleavage

摘要

Seventh-pandemic Vibrio cholerae strains contain two pathogenicity islands that encode the DNA defense modules DdmABC and DdmDE. In this study, we used cryogenic electron microscopy to determine the mechanistic basis for plasmid defense by DdmDE. The helicase-nuclease DdmD adopts an autoinhibited dimeric architecture. The prokaryotic Argonaute protein DdmE uses a DNA guide to target plasmid DNA. The structure of the DdmDE complex, validated by in vivo mutational studies, shows that DNA binding by DdmE triggers disassembly of the DdmD dimer and loading of monomeric DdmD onto the nontarget DNA strand. In vitro studies indicate that DdmD translocates in the 5 '-to-3 ' direction, while partially degrading the plasmid DNA. These findings provide critical insights into the mechanism of DdmDE systems in plasmid elimination.