Abstract：
:Bacteria have obtained a variety of resistance mechanisms including toxin-antitoxin (TA) systems against bacteriophages (phages), whereas phages have also evolved to overcome bacterial anti-phage mechanisms. Dmd from T4 phage can suppress the toxicities of homologous toxins LsoA and RnlA from Escherichia coli, representing the first example of a phage antitoxin against multiple bacterial toxins in known TA systems. Here, the crystal structure of LsoA-Dmd complex showed Dmd is inserted into the deep groove between the N-terminal repeated domain (NRD) and the Dmd-binding domain (DBD) of LsoA. The NRD shifts significantly from a 'closed' to an 'open' conformation upon Dmd binding. Site-directed mutagenesis of Dmd revealed the conserved residues (W31 and N40) are necessary for LsoA binding and the toxicity suppression as determined by pull-down and cell toxicity assays. Further mutagenesis identified the conserved Dmd-binding residues (R243, E246 and R305) of LsoA are vital for its toxicity, and suggested Dmd and LsoB may possess different inhibitory mechanisms against LsoA toxicity. Our structure-function studies demonstrate Dmd can recognize LsoA and inhibit its toxicity by occupying the active site possibly via substrate mimicry. These findings have provided unique insights into the defense and counter-defense mechanisms between bacteria and phages in their co-evolution.
journal_name
Mol Microbioljournal_title
Molecular microbiologyauthors
Wan H,Otsuka Y,Gao ZQ,Wei Y,Chen Z,Masuda M,Yonesaki T,Zhang H,Dong YHdoi
10.1111/mmi.13420subject
Has Abstractpub_date
2016-09-01 00:00:00pages
757-69issue
5eissn
0950-382Xissn
1365-2958journal_volume
101pub_type
杂志文章abstract：:The non-essential RGD1 gene from Saccharomyces cerevisiae encodes a protein that has been characterized in vitro as a Rho GTPase activating protein (RhoGAP) for the Rho3 and Rho4 proteins. Rgd1p, which displays a conserved FCH-coiled coil-Rho-GAP domain organization, showed a patch-like distribution in the cell, inclu...
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更新日期：2000-06-01 00:00:00
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pub_type： 杂志文章
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更新日期：2007-07-01 00:00:00
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更新日期：2002-10-01 00:00:00
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journal_title：Molecular microbiology
pub_type： 杂志文章
doi：10.1111/j.1365-2958.1995.tb02377.x
更新日期：1995-02-01 00:00:00
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pub_type： 杂志文章
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更新日期：1999-04-01 00:00:00
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journal_title：Molecular microbiology
pub_type： 杂志文章
doi：10.1111/j.1365-2958.1995.mmi_17040769.x
更新日期：1995-08-01 00:00:00
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journal_title：Molecular microbiology
pub_type： 杂志文章
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更新日期：1993-10-01 00:00:00
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pub_type： 杂志文章
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更新日期：2005-12-01 00:00:00
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pub_type： 杂志文章
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更新日期：2006-09-01 00:00:00
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doi：10.1111/j.1365-2958.2008.06170.x
更新日期：2008-04-01 00:00:00
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journal_title：Molecular microbiology
pub_type： 杂志文章
doi：10.1111/mmi.14618
更新日期：2020-10-04 00:00:00
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journal_title：Molecular microbiology
pub_type： 杂志文章
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更新日期：2000-02-01 00:00:00
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journal_title：Molecular microbiology
pub_type： 杂志文章
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更新日期：2014-05-01 00:00:00
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journal_title：Molecular microbiology
pub_type： 杂志文章
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更新日期：2005-08-01 00:00:00
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journal_title：Molecular microbiology
pub_type： 杂志文章
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journal_title：Molecular microbiology
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journal_title：Molecular microbiology
pub_type： 杂志文章
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journal_title：Molecular microbiology
pub_type： 杂志文章
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journal_title：Molecular microbiology
pub_type： 杂志文章
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更新日期：2015-08-01 00:00:00
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journal_title：Molecular microbiology
pub_type： 杂志文章
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更新日期：2006-11-01 00:00:00
