VapBC
Encyclopedia
VapBC is the largest family of type II toxin-antitoxin system
genetic loci
in prokaryote
s. VapBC operon
s 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.
First discovered in 1992, vapBC loci are now thought make up around 37–42% of all type II toxin-antitoxin systems.
polypeptide, while vagD encoded a smaller 10kDa protein. Their open reading frame
s were found to overlap by a single nucleotide
; suggesting they were translated together, and at a constant molar
ratio.
, Mycobacterium tuberculosis
and Piscirickettsia salmonis. The loci have been described as "surprisingly abundant, especially in Archaea"—vapBC family members made up 37% of all TA families identified by one bioinformatics search and 42% of those found by another.
Bioinformatics
searches have discovered vapBC homologues on both chromosome
s and plasmid
s, and often in high copy number per cell. They are less common, however, in firmicutes
and cyanobacteria. Genomes with high numbers of vapBC loci include: M. tuberculosis with 45 predicted loci; S.tokodaii with 25; S.solfataricus with 23 and Sinorhizobium meliloti
with 21.
s in cleaving RNA
molecules, thereby reducing the rate of translation. In the bacteria Shigella flexneri
and Salmonella enterica
, VapC toxins have been shown to perform specific cleavage of a tRNA, but in other bacteria the RNA cleavage may be less specific.
VapC is strongly inhibited by direct protein interaction with VapB, its cognate antitoxin. The toxin-antitoxin complex is thought to autoregulate its own operon, repressing transcription of both components through a DNA-binding domain in VapB.
In some organisms, vapBC loci have been assigned other potential functions. In the hyperthermophilic
archaean Sulfolobus solfataricus
, for example, a vapBC gene cassette is though to regulate heat shock
response.
Toxin-antitoxin system
A toxin-antitoxin system is a set of two or more closely linked genes that together encode both a protein 'poison' and a corresponding 'antidote'. When these systems are contained on plasmids – transferable genetic elements – they ensure that only the daughter cells that inherit the plasmid...
genetic loci
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
in prokaryote
Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
s. VapBC operon
Operon
In genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo trans-splicing to create...
s consist of two genes: VapC encodes a toxic PilT N-terminus
PIN domain
In molecular biology the PIN domain is a protein domain that is about 130 amino acids in length. The PIN domain was named after its identification in the N-terminus of the PilT protein . PIN domains function as nuclease enzymes that cleave single stranded RNA in a sequence dependent manner.PIN...
(PIN) domain, and VapB encodes a matching antitoxin. The toxins in this family are thought to perform RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
cleavage, which is inhibited by the co-expression of the antitoxin, in a manner analogous to a poison and antidote.
First discovered in 1992, vapBC loci are now thought make up around 37–42% of all type II toxin-antitoxin systems.
Discovery
Following the discoveries of two other type II toxin-antitoxin systems, the first vapBC system to be characterised was found in Salmonella dublin strain G19 in 1992. It was characterised as a system for ensuring that all daughter cells contained a copy of the plasmid encoding the vapBC locus. The two components of this plasmidic system were originally named vagC and vagD (virulence-associated gene) for the toxin and antitoxin genes respectively. VagC was predicted to encode a 12kDaAtomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...
polypeptide, while vagD encoded a smaller 10kDa protein. Their open reading frame
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...
s were found to overlap by a single nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
; suggesting they were translated together, and at a constant molar
Mole (unit)
The mole is a unit of measurement used in chemistry to express amounts of a chemical substance, defined as an amount of a substance that contains as many elementary entities as there are atoms in 12 grams of pure carbon-12 , the isotope of carbon with atomic weight 12. This corresponds to a value...
ratio.
Distribution
VapBC operons have been found in distantly related prokaryotes, including the pathogens Leptospira interrogansLeptospira interrogans
Leptospira interrogans is a species of Leptospira, which is a gram negative obligate aerobe spirochete, with periplasmic flagellum. The two important pathogenic serovars from this species are Canicola and Icterohaemorrhagiae. These reside in alkaline water, alkaline soil and can survive in these...
, Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
and Piscirickettsia salmonis. The loci have been described as "surprisingly abundant, especially in Archaea"—vapBC family members made up 37% of all TA families identified by one bioinformatics search and 42% of those found by another.
Bioinformatics
Bioinformatics
Bioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
searches have discovered vapBC homologues on both chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s and plasmid
Plasmid
In microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...
s, and often in high copy number per cell. They are less common, however, in firmicutes
Firmicutes
The Firmicutes are a phylum of bacteria, most of which have Gram-positive cell wall structure. A few, however, such as Megasphaera, Pectinatus, Selenomonas and Zymophilus, have a porous pseudo-outer-membrane that causes them to stain Gram-negative...
and cyanobacteria. Genomes with high numbers of vapBC loci include: M. tuberculosis with 45 predicted loci; S.tokodaii with 25; S.solfataricus with 23 and Sinorhizobium meliloti
Sinorhizobium meliloti
Sinorhizobium meliloti is a Gram-negative nitrogen-fixing bacterium . It forms a symbiotic relationship with legumes from the genera Medicago, Melilotus and Trigonella, including the model legume Medicago truncatula. This symbiosis results in a new plant organ termed a root nodule. The S...
with 21.
Function(s)
VapC toxins, specifically the PIN domains, act as ribonucleaseRibonuclease
Ribonuclease is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...
s in cleaving RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
molecules, thereby reducing the rate of translation. In the bacteria Shigella flexneri
Shigella flexneri
Shigella flexneri is a species of Gram-negative bacteria in the genus Shigella that can cause diarrhea in humans. There are several different serogroups of Shigella; S. flexneri belongs to group B. S. flexneri infections can usually be treated with antibiotics although some strains have become...
and Salmonella enterica
Salmonella enterica
Salmonella enterica is a rod-shaped flagellated, facultative anaerobic, Gram-negative bacterium, and a member of the genus Salmonella.- Epidemiology :...
, VapC toxins have been shown to perform specific cleavage of a tRNA, but in other bacteria the RNA cleavage may be less specific.
VapC is strongly inhibited by direct protein interaction with VapB, its cognate antitoxin. The toxin-antitoxin complex is thought to autoregulate its own operon, repressing transcription of both components through a DNA-binding domain in VapB.
In some organisms, vapBC loci have been assigned other potential functions. In the hyperthermophilic
Hyperthermophile
A hyperthermophile is an organism that thrives in extremely hot environments— from 60 degrees C upwards. An optimal temperature for the existence of hyperthermophiles is above 80°C . Hyperthermophiles are a subset of extremophiles, micro-organisms within the domain Archaea, although some bacteria...
archaean Sulfolobus solfataricus
Sulfolobus
Sulfolobus is a genus of microorganism in the family Sulfolobaceae. It belongs to the archea domain.Sulfolobus species grow in volcanic springs with optimal growth occurring at pH 2-3 and temperatures of 75-80 °C, making them acidophiles and thermophiles respectively...
, for example, a vapBC gene cassette is though to regulate heat shock
Heat shock
In biochemistry, heat shock is the effect of subjecting a cell to a higher temperature than that of the ideal body temperature of the organism from which the cell line was derived.-Heat shock response:...
response.