Molecular mechanism of plasmid elimination by the DdmDE defense system

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2024-06-13 DOI:10.1126/science.adq0534

Luuk Loeff, David W. Adams, Christelle Chanez, Sandrine Stutzmann, Laurie Righi, Melanie Blokesch, Martin Jinek

引用次数: 0

Abstract

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.

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DdmDE防御系统消除质粒的分子机制

第七次大流行的霍乱弧菌菌株含有两个致病性岛，分别编码 DNA 防御模块 DdmABC 和 DdmDE。在这里，我们利用低温电子显微镜揭示了 DdmDE 防御质粒的机理基础。DdmD 螺旋酶-核酸酶的结构显示，它采用了一种自动抑制的二聚体结构。原核生物的Argonaute蛋白DdmE利用DNA向导靶向质粒DNA。经体内突变研究验证的 DdmDE 复合物结构表明，DdmE 与 DNA 结合会触发 DdmD 二聚体的解体，并将单体 DdmD 加载到非目标 DNA 链上。体外研究显示，DdmD 在 5′-3′方向上进行转运，同时部分降解质粒 DNA。这些发现为 DdmDE 系统消除质粒的机制提供了重要启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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