BtoxDB: A comprehensive database of protein structural data on toxin–antitoxin systems

Barbosa, Luiz Carlos Bertucci; Garrido, Saulo Santesso; Marchetto, Reinaldo

doi:10.1016/j.compbiomed.2015.01.010

Cited by 16 publications

(8 citation statements)

References 33 publications

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“…The cognate toxin and antitoxin of a TA system are small proteins encoded by two genes organized in one operon (36). The activity of the toxin can be neutralized by forming a protein complex with its cognate antitoxin (30,37).…”

Section: Discussionmentioning

confidence: 99%

Physical and Functional Interplay between MazF ₁ ^Bif and Its Noncognate Antitoxins from Bifidobacterium longum

Wei

Yang

et al. 2017

Appl Environ Microbiol

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strain JDM301, a widely used commercial strain in China, encodes at least two MazEF-like modules and one RelBE-like toxin-antitoxin (TA) system in its chromosome, designated MazEF, MazEF, and RelBE, respectively. Bacterial TA systems play an important role in several stress responses, but the relationship between these TA systems is largely unknown. In this study, the interactions between MazF and MazE or RelB were assessed in strain JDM301. MazF caused the degradation of mRNA, and its toxicity was inhibited by forming a protein complex with its cognate antitoxin, MazE Notably, MazF toxicity was also partially neutralized when jointly expressed with noncognate antitoxin MazE or RelB Our results show that the two noncognate antitoxins also inhibited mRNA degradation caused by MazF toxin. Furthermore, the physical interplay between MazF and its noncognate antitoxins was confirmed by immunoprecipitation. These results suggest that MazF can arrest cell growth and that MazF toxicity can be neutralized by its cognate and noncognate antitoxins. These results imply that JDM301 uses a sophisticated toxin-antitoxin interaction network to alter its physiology when coping with environmental stress. Although toxin-antitoxin (TA) systems play an important role in several stress responses, the regulatory mechanisms of multiple TA system homologs in the bacterial genome remain largely unclear. In this study, the relationships between MazEF and the other two TA systems of strain JDM301 were explored, and the interactions between MazF and MazE or RelB were characterized. In addition, the mRNA degradation activity of MazF was demonstrated. In particular, the interaction of the toxin with noncognate antitoxins was shown, even between different TA families (MazF toxin and RelB antitoxin) in JDM301. This work provides insight into the regulatory mechanisms of TA systems implicated in the stress responses of bifidobacteria.

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Section: Discussionmentioning

confidence: 99%

Physical and Functional Interplay between MazF ₁ ^Bif and Its Noncognate Antitoxins from Bifidobacterium longum

Wei

Yang

et al. 2017

Appl Environ Microbiol

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“… Antitoxin grouping is based on Leplae et al [ 119 ] and consistent with that found by Arbing et al [ 120 ]. ¥ Toxin Antitoxin Database [ 101 ]; ▯ Number of entries in the Protein Families Database [ 121 ]; ❖ Database of toxin-antitoxin structural depositions database [ 122 ]; § Alignments were constructed using the ClustalW algorithm, and were visualized as a consensus sequence with the online server WebLogo [ 123 ] and with CLC Genomics Workbench© 8.0.3 [ 124 ]. N.D. , no data available.…”

Section: Figurementioning

confidence: 99%

Toxin-Antitoxin Modules Are Pliable Switches Activated by Multiple Protease Pathways

Muthuramalingam

White

Bourne

2016

Toxins

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Toxin-antitoxin (TA) modules are bacterial regulatory switches that facilitate conflicting outcomes for cells by promoting a pro-survival phenotypic adaptation and/or by directly mediating cell death, all through the toxin activity upon degradation of antitoxin. Intensive study has revealed specific details of TA module functions, but significant gaps remain about the molecular details of activation via antitoxin degradation used by different bacteria and in different environments. This review summarizes the current state of knowledge about the interaction of antitoxins with cellular proteases Lon and ClpP to mediate TA module activation. An understanding of these processes can answer long-standing questions regarding stochastic versus specific activation of TA modules and provide insight into the potential for manipulation of TA modules to alter bacterial growth.

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“…The product of the antitoxin gene, which can be either RNA or protein, is usually less stable compared to the toxin protein. Depending on the mechanism by which the antitoxin neutralizes the toxin, TAs have been categorized into six different types: (i) Type I, in which the antitoxin mRNA binds to its complementary toxin mRNA to prevent translation of the toxin gene; (ii) Type II, the antitoxin is a protein that forms a stable complex with the toxin protein and blocking the active site of the toxin under normal growth conditions; (iii) Type III, the antitoxin is an RNA with multiple tandem repeats that binds directly to the toxin protein rendering the toxin inactive; (iv) Type IV, the antitoxin protein does not bind to the toxin, but antagonize the toxin effect by competing for binding to the cellular target; and (v) Type V, the antitoxin protein is an RNase that cleaves directly its cognate toxin mRNA (Alonso et al, 2007 ; Hayes and Van Melderen, 2011 ; Masuda et al, 2012 ; Cataudella et al, 2013 ; Unterholzner et al, 2013 ; Barbosa et al, 2015 ). A likely new type of TA system (a possible type VI) was recently discovered in Caulobater crescentus where both the SocA antitoxin and SocB toxin are proteins, as in types II and IV TA systems.…”

Section: Introductionmentioning

confidence: 99%

Keeping the Wolves at Bay: Antitoxins of Prokaryotic Type II Toxin-Antitoxin Systems

Chan

Espinosa

Yeo

2016

Front. Mol. Biosci.

129

121

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In their initial stages of discovery, prokaryotic toxin-antitoxin (TA) systems were confined to bacterial plasmids where they function to mediate the maintenance and stability of usually low- to medium-copy number plasmids through the post-segregational killing of any plasmid-free daughter cells that developed. Their eventual discovery as nearly ubiquitous and repetitive elements in bacterial chromosomes led to a wealth of knowledge and scientific debate as to their diversity and functionality in the prokaryotic lifestyle. Currently categorized into six different types designated types I–VI, type II TA systems are the best characterized. These generally comprised of two genes encoding a proteic toxin and its corresponding proteic antitoxin, respectively. Under normal growth conditions, the stable toxin is prevented from exerting its lethal effect through tight binding with the less stable antitoxin partner, forming a non-lethal TA protein complex. Besides binding with its cognate toxin, the antitoxin also plays a role in regulating the expression of the type II TA operon by binding to the operator site, thereby repressing transcription from the TA promoter. In most cases, full repression is observed in the presence of the TA complex as binding of the toxin enhances the DNA binding capability of the antitoxin. TA systems have been implicated in a gamut of prokaryotic cellular functions such as being mediators of programmed cell death as well as persistence or dormancy, biofilm formation, as defensive weapons against bacteriophage infections and as virulence factors in pathogenic bacteria. It is thus apparent that these antitoxins, as DNA-binding proteins, play an essential role in modulating the prokaryotic lifestyle whilst at the same time preventing the lethal action of the toxins under normal growth conditions, i.e., keeping the proverbial wolves at bay. In this review, we will cover the diversity and characteristics of various type II TA antitoxins. We shall also look into some interesting deviations from the canonical type II TA systems such as tripartite TA systems where the regulatory role is played by a third party protein and not the antitoxin, and a unique TA system encoding a single protein with both toxin as well as antitoxin domains.

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BtoxDB: A comprehensive database of protein structural data on toxin–antitoxin systems

Abstract: The compilation of all protein structural data on TA systems in one platform is highly useful for researchers interested in this content. BtoxDB is publicly available at http://www.gurupi.uft.edu.br/btoxdb.

Cited by 16 publications

References 33 publications

Physical and Functional Interplay between MazF ₁ ^Bif and Its Noncognate Antitoxins from Bifidobacterium longum

Physical and Functional Interplay between MazF ₁ ^Bif and Its Noncognate Antitoxins from Bifidobacterium longum

Toxin-Antitoxin Modules Are Pliable Switches Activated by Multiple Protease Pathways

Keeping the Wolves at Bay: Antitoxins of Prokaryotic Type II Toxin-Antitoxin Systems

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BtoxDB: A comprehensive database of protein structural data on toxin–antitoxin systems

Abstract: The compilation of all protein structural data on TA systems in one platform is highly useful for researchers interested in this content. BtoxDB is publicly available at http://www.gurupi.uft.edu.br/btoxdb.

Cited by 16 publications

References 33 publications

Physical and Functional Interplay between MazF 1 Bif and Its Noncognate Antitoxins from Bifidobacterium longum

Physical and Functional Interplay between MazF 1 Bif and Its Noncognate Antitoxins from Bifidobacterium longum

Toxin-Antitoxin Modules Are Pliable Switches Activated by Multiple Protease Pathways

Keeping the Wolves at Bay: Antitoxins of Prokaryotic Type II Toxin-Antitoxin Systems

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Physical and Functional Interplay between MazF ₁ ^Bif and Its Noncognate Antitoxins from Bifidobacterium longum

Physical and Functional Interplay between MazF ₁ ^Bif and Its Noncognate Antitoxins from Bifidobacterium longum