Cleavage of the antitoxin of the parD toxin–antitoxin system is determined by the ClpAP protease and is modulated by the relative ratio of the toxin and the antitoxin

Diago-Navarro, Elizabeth; Hernández‐Arriaga, Ana M.; Kubik, Slawomir; Konieczny, Igor; Dı́az-Orejas, Ramón

doi:10.1016/j.plasmid.2013.01.010

Cited by 28 publications

(24 citation statements)

References 38 publications

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“…A drastic, rapid reduction in the antitoxin level was observed; the major degradation of Epsilon occurred in less than 15 min. We estimated that Epsilon is degraded by ClpXP with a T1 ⁄ 2 of ϳ8 min in vitro, which is similar to the degradation of Kis antitoxin by the ClpAP protease in in vitro proteolysis assays (58).…”

Section: Discussionsupporting

confidence: 52%

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The ClpXP Protease Is Responsible for the Degradation of the Epsilon Antidote to the Zeta Toxin of the Streptococcal pSM19035 Plasmid

Brzozowska

Zielenkiewicz

2014

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 52%

“…Antitoxin proteolysis has been examined in many E. coli TA systems, generally only using in vivo analysis. In the cases of the RelB (57), CcdA (3), HipB (9), and Kis (58) antitoxins, this process has been further elucidated using in vitro degradation assays. Still, little is known in this field for bacteria other than E. coli.…”

Section: Discussionmentioning

confidence: 99%

The ClpXP Protease Is Responsible for the Degradation of the Epsilon Antidote to the Zeta Toxin of the Streptococcal pSM19035 Plasmid

Brzozowska

Zielenkiewicz

2014

Journal of Biological Chemistry

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“…The DinJ TEV substituted loop 5 is resistant to Lon degradation strongly suggesting loop 5 as important for initial Lon recognition. The binding of toxins to antitoxins have been shown to hinder access to proteolytic sites in the context of certain toxin–antitoxin complexes including CcdBA, Kid‐Kis and the YoeB‐YefM (Bernard et al ., ; Van Melderen et al ., ; Kamada and Hanaoka, ; Diago‐Navarro et al ., ). However, our studies indicate that YafQ binding does not prevent Lon from degrading DinJ.…”

Section: Discussionmentioning

confidence: 97%

Importance of the E. coli DinJ antitoxin carboxy terminus for toxin suppression and regulated proteolysis

Ruangprasert

Maehigashi

Miles

et al. 2017

Molecular Microbiology

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Toxin-antitoxin genes play important roles in the regulation of bacterial growth during stress. One response to stress is selective proteolysis of antitoxin proteins which releases their cognate toxin partners causing rapid inhibition of growth. The features of toxin-antitoxin complexes that are important to inhibit toxin activity as well as to release the active toxin remain elusive. Furthermore, it is unclear how antitoxins are selected for proteolysis by cellular proteases. Here, we test the minimal structural requirements of the Escherichia coli DinJ antitoxin to suppress its toxin partner, YafQ. We find that DinJ-YafQ complex formation is critically dependent on the last ten C-terminal residues of DinJ. However, deletion of these 10 DinJ residues has little effect on transcriptional autorepression suggesting that the YafQ toxin is not a critical component of the repression complex in contrast to other toxin-antitoxin systems. We further demonstrate that loop 5 preceding these ten C-terminal residues is important for Lon-mediated proteolysis. These results provide important insights into the critical interactions between toxin-antitoxin pairs necessary to inhibit toxin activity and the regulated proteolysis of antitoxins.

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“…For example, CcdA is actively and constitutively degraded by the Lon protease (107). Other antitoxins, like Kis, from the parD system or Phd were shown to be degraded in a similar way by the ClpAP and ClpXP proteases, respectively (108,109). Therefore, constitutive proteolysis of plasmid-encoded antitoxins appears as a rule since it supposedly allows the liberation of toxin molecules in plasmid-free segregants.…”

Section: Activation Of Ta Systems: From Regulation To Phenotypesmentioning

confidence: 99%

Type II Toxin-Antitoxin Systems: Evolution and Revolutions

2020

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Type II toxin-antitoxin (TA) systems are small genetic elements composed of a toxic protein and its cognate antitoxin protein, the latter counteracting the toxicity of the former. While TA systems were initially discovered on plasmids, functioning as addiction modules through a phenomenon called postsegregational killing, they were later shown to be massively present in bacterial chromosomes, often in association with mobile genetic elements. Extensive research has been conducted in recent decades to better understand the physiological roles of these chromosomally encoded modules and to characterize the conditions leading to their activation. The diversity of their proposed roles, ranging from genomic stabilization and abortive phage infection to stress modulation and antibiotic persistence, in conjunction with the poor understanding of TA system regulation, resulted in the generation of simplistic models, often refuted by contradictory results. This review provides an epistemological and critical retrospective on TA modules and highlights fundamental questions concerning their roles and regulations that still remain unanswered. FIG 1 Type II TA systems, postsegregational killing and distribution. (A) Nonviable segregant or postsegregational killing model. TA genes, as well as proteins, are represented in red (toxins) and green (antitoxins).Rectangles denote TA genes encoded on a plasmid, and round shapes denote TA proteins produced from these genes. A TA-encoding plasmid can be lost during division in a way that one of the daughter cells does not inherit a plasmid copy. In these cells, TA proteins cannot be replenished due to the absence of TA genes. Since the antitoxin is degraded while its cognate toxin is stable, the free toxin concentration will increase, exert its activity, and, in time, induce cell death, therefore killing plasmid-free segregants. (B) Distribution of type II TA systems in various E. coli reference strains generated by TAfinder (23). Asterisks indicate systems that were not validated experimentally. Parentheses include name of the prophage a TA is encoded on when applicable. The strains are MG1655 (NCBI U00096.3), a common lab strain from phylogroup A; W (CP002967.1), a soil isolate from phylogroup B1; EDL933 (AE005174.2), an enterohemorrhagic pathogen from phylogroup E; and UTI89 (CP000243.1), a uropathogen from phylogroup B2. No TA systems are conserved within these four distantly related E. coli strains.

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Cleavage of the antitoxin of the parD toxin–antitoxin system is determined by the ClpAP protease and is modulated by the relative ratio of the toxin and the antitoxin

Cited by 28 publications

References 38 publications

The ClpXP Protease Is Responsible for the Degradation of the Epsilon Antidote to the Zeta Toxin of the Streptococcal pSM19035 Plasmid

The ClpXP Protease Is Responsible for the Degradation of the Epsilon Antidote to the Zeta Toxin of the Streptococcal pSM19035 Plasmid

Importance of the E. coli DinJ antitoxin carboxy terminus for toxin suppression and regulated proteolysis

Type II Toxin-Antitoxin Systems: Evolution and Revolutions

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