ParDE type II toxin-antitoxin system

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ParE toxin of type II Toxin-anittoxin system
PDB 1wmi EBI.jpg
crystal structure of archaeal rele-relb complex from pyrococcus horikoshii ot3
Identifiers
SymbolParE_toxin
Pfam PF05016
Pfam clan CL0136
InterPro IPR007712
ParD
Identifiers
SymbolParD
Pfam PF09386
Pfam clan CL0057
InterPro IPR018985

The parDE type II toxin-antitoxin system is one example of the bacterial toxin-antitoxin (TA) systems that encode two proteins, one a potent inhibitor of cell proliferation (toxin) and the other its specific antidote (antitoxin). These systems preferentially guarantee growth of plasmid-carrying daughter cells in a bacterial population by killing newborn bacteria that have not inherited a plasmid copy at cell division (post-segregational killing). [1]

ParD is a plasmid anti-toxin that forms a ribbon-helix-helix DNA binding structure. [2] It stabilises plasmids by inhibiting ParE toxicity in cells that express ParD and ParE. ParD forms a dimer and also regulates its own promoter (parDE). As with CcdB the toxin target is DNA gyrase. [3] Induction of ParE toxin results in inhibition of cell division but not cell growth.

The parD and ccD systems are found to be strikingly similar in terms of their structures and actions. The antitoxin protein of each system interacts with its cognate toxin to neutralise the activity of the toxin and in the process the complex of the two becomes an efficient transcription repressor. [4]

Related Research Articles

Pathogenicity islands (PAIs), as termed in 1990, are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. Pathogenicity islands are found in both animal and plant pathogens. Additionally, PAIs are found in both gram-positive and gram-negative bacteria. They are transferred through horizontal gene transfer events such as transfer by a plasmid, phage, or conjugative transposon. Therefore, PAIs contribute to microorganisms' ability to evolve.

RecA DNA repair protein

RecA is a 38 kilodalton protein essential for the repair and maintenance of DNA. A RecA structural and functional homolog has been found in every species in which one has been seriously sought and serves as an archetype for this class of homologous DNA repair proteins. The homologous protein is called RAD51 in eukaryotes and RadA in archaea.

Repressor lexA

Repressor LexA or LexA is a transcriptional repressor that represses SOS response genes coding primarily for error-prone DNA polymerases, DNA repair enzymes and cell division inhibitors. LexA forms de facto a two-component regulatory system with RecA, which senses DNA damage at stalled replication forks, forming monofilaments and acquiring an active conformation capable of binding to LexA and causing LexA to cleave itself, in a process called autoproteolysis.

Colicin

A colicin is a type of bacteriocin produced by and toxic to some strains of Escherichia coli. Colicins are released into the environment to reduce competition from other bacterial strains. Colicins bind to outer membrane receptors, using them to translocate to the cytoplasm or cytoplasmic membrane, where they exert their cytotoxic effect, including depolarisation of the cytoplasmic membrane, DNase activity, RNase activity, or inhibition of murein synthesis.

Addiction modules are toxin-antitoxin systems. Each consists of a pair of genes that specify two components: a stable toxin and an unstable antitoxin that interferes with the lethal action of the toxin. Found first in E. coli on low copy number plasmids, addiction modules are responsible for a process called the postsegregational killing effect. When bacteria lose these plasmid(s), the cured cells are selectively killed because the unstable antitoxin is degraded faster than the more stable toxin. The term "addiction" is used because the cell depends on the de novo synthesis of the antitoxin for cell survival. Thus, addiction modules are implicated in maintaining the stability of extrachromosomal elements.

Sib RNA

Sib RNA refers to a group of related non-coding RNA. They were originally named QUAD RNA after they were discovered as four repeat elements in Escherichia coli intergenic regions. The family was later renamed Sib when it was discovered that the number of repeats is variable in other species and in other E. coli strains.

Hok/sok system

The hok/sok system is a postsegregational killing mechanism employed by the R1 plasmid in Escherichia coli. It was the first type I toxin-antitoxin pair to be identified through characterisation of a plasmid-stabilising locus. It is a type I system because the toxin is neutralised by a complementary RNA, rather than a partnered protein.

Prokaryotic cytoskeleton

The prokaryotic cytoskeleton is the collective name for all structural filaments in prokaryotes. It was once thought that prokaryotic cells did not possess cytoskeletons, but advances in visualization technology and structure determination led to the discovery of filaments in these cells in the early 1990s. Not only have analogues for all major cytoskeletal proteins in eukaryotes been found in prokaryotes, cytoskeletal proteins with no known eukaryotic homologues have also been discovered. Cytoskeletal elements play essential roles in cell division, protection, shape determination, and polarity determination in various prokaryotes.

Segrosomes are protein complexes that ensure accurate segregation (partitioning) of plasmids or chromosomes during bacterial cell division.

AB toxin

The AB toxins are two-component protein complexes secreted by a number of pathogenic bacteria. They can be classified as Type III toxins because they interfere with internal cell function. They are named AB toxins due to their components: the "A" component is usually the "active" portion, and the "B" component is usually the "binding" portion. The "A" subunit possesses enzyme activity, and is transferred to the host cell following a conformational change in the membrane-bound transport "B" subunit. These proteins consist of two independent polypeptides, which correspond to the A/B subunit moieties. The enzyme component (A) enters the cell through endosomes produced by the oligomeric binding/translocation protein (B), and prevents actin polymerisation through ADP-ribosylation of monomeric G-actin.

TisB-IstR toxin-antitoxin system

The TisB-IstR toxin-antitoxin system is the first known toxin-antitoxin system which is induced by the SOS response in response to DNA damage.

Toxin-antitoxin system

A toxin-antitoxin system is a set of two or more closely linked genes that together encode both a "toxin" protein and a corresponding "antitoxin". Toxin-antitoxin systems are widely distributed in prokaryotes, and organisms often have them in multiple copies. When these systems are contained on plasmids – transferable genetic elements – they ensure that only the daughter cells that inherit the plasmid survive after cell division. If the plasmid is absent in a daughter cell, the unstable antitoxin is degraded and the stable toxic protein kills the new cell; this is known as 'post-segregational killing' (PSK).

LdrD-RdlD toxin-antitoxin system

RdlD RNA is a family of small non-coding RNAs which repress the protein LdrD in a type I toxin-antitoxin system. It was discovered in Escherichia coli strain K-12 in a long direct repeat (LDR) named LDR-D. This locus encodes two products: a 35 amino acid peptide toxin (ldrD) and a 60 nucleotide RNA antitoxin. The 374nt toxin mRNA has a half-life of around 30 minutes while rdlD RNA has a half-life of only 2 minutes. This is in keeping with other type I toxin-antitoxin systems.

FlmA-FlmB toxin-antitoxin system

The FlmA-FlmB toxin-antitoxin system consists of FlmB RNA, a family of non-coding RNAs and the protein toxin FlmA. The FlmB RNA transcript is 100 nucleotides in length and is homologous to sok RNA from the hok/sok system and fulfills the identical function as a post-segregational killing (PSK) mechanism.

par stability determinant

The par stability determinant is a 400 bp locus of the pAD1 plasmid which encodes a type I toxin-antitoxin system in Enterococcus faecalis. It was the first such plasmid addiction module to be found in gram-positive bacteria.

vapBC

VapBC is the largest family of type II toxin-antitoxin system genetic loci in prokaryotes. VapBC operons consist of two genes: VapC encodes a toxic PilT N-terminus (PIN) domain, and VapB encodes a matching antitoxin. The toxins in this family are thought to perform RNA cleavage, which is inhibited by the co-expression of the antitoxin, in a manner analogous to a poison and antidote.

Iron dependent repressor

In molecular biology, the iron dependent repressors are a family of bacterial and archaeal transcriptional repressors.

Zeta toxin protein domain

In molecular biology, the protein domain Zeta (ζ) toxin refers to a protein domain found in prokaryotes, which acts as a UDP-N-acetylglucosamine kinase. Its function is to inhibit cell wall biosynthesis and it may act as a bactericide in nature. It is also thought that Zeta toxin induces reversible protective dormancy and permeation to propidium iodide (PI).

CcdA/CcdB Type II Toxin-antitoxin system

The CcdA/CcdB Type II Toxin-antitoxin system is one example of the bacterial toxin-antitoxin (TA) systems that encode two proteins, one a potent inhibitor of cell proliferation (toxin) and the other its specific antidote (antitoxin). These systems preferentially guarantee growth of plasmid-carrying daughter cells in a bacterial population by killing newborn bacteria that have not inherited a plasmid copy at cell division.

A plasmid partition system is a mechanism that ensures the stable inheritance of plasmids during bacterial cell division. Each plasmid has its independent replication system which controls the number of copies of the plasmid in a cell. The higher the copy number is, the more likely the two daughter cells will contain the plasmid. Generally, each molecule of plasmid diffuses randomly, so the probability of having a plasmid-less daughter cell is 21−N, where N is the number of copies. For instance, if there are 2 copies of a plasmid in a cell, there is a 50% chance of having one plasmid-less daughter cell. However, high-copy number plasmids have a cost for the hosting cell. This metabolic burden is lower for low-copy plasmids, but those have a higher probability of plasmid loss after a few generations. To control vertical transmission of plasmids, in addition to controlled-replication systems, bacterial plasmids use different maintenance strategies, such as multimer resolution systems, post-segregational killing systems, and partition systems.

References

  1. Jensen RB, Gerdes K (1995). "Programmed cell death in bacteria: proteic plasmid stabilization systems". Mol Microbiol. 17 (2): 205–10. doi:10.1111/j.1365-2958.1995.mmi_17020205.x. PMID   7494469.
  2. Oberer M, Zangger K, Prytulla S, Keller W (January 2002). "The anti-toxin ParD of plasmid RK2 consists of two structurally distinct moieties and belongs to the ribbon-helix-helix family of DNA-binding proteins". Biochem. J. 361 (Pt 1): 41–7. doi:10.1042/0264-6021:3610041. PMC   1222296 . PMID   11743881.
  3. Fiebig A, Castro Rojas CM, Siegal-Gaskins D, Crosson S (2010). "Interaction specificity, toxicity and regulation of a paralogous set of ParE/RelE-family toxin-antitoxin systems". Mol Microbiol. 77 (1): 236–51. doi:10.1111/j.1365-2958.2010.07207.x. PMC   2907451 . PMID   20487277.
  4. Smith AB, López-Villarejo J, Diago-Navarro E, Mitchenall LA, Barendregt A, Heck AJ, et al. (2012). "A Common Origin for the Bacterial Toxin-Antitoxin Systems parD and ccd, Suggested by Analyses of Toxin/Target and Toxin/Antitoxin Interactions". PLOS ONE. 7 (9): e46499. doi:10.1371/journal.pone.0046499. PMC   3460896 . PMID   23029540.
This article incorporates text from the public domain Pfam and InterPro: IPR018985
This article incorporates text from the public domain Pfam and InterPro: IPR007712