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0  structures 0  species 0  sequences

Motif: vapC_target (RM00031)

Description: vapC ribonuclease target

Summary

Wikipedia annotation Edit Wikipedia article

The Rfam group coordinates the annotation of Rfam data in Wikipedia. This motif is described by a Wikipedia entry entitled VapBC. More...

Crystallographic tertiary structure of a VapC toxin PIN domain.

VapBC (virulence associated proteins B and C) is the largest family of type II toxin-antitoxin system genetic loci in prokaryotes.[1] VapBC operons consist of two genes: VapC encodes a toxic PilT N-terminus (PIN) domain, and VapB encodes a matching antitoxin.[2] 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.[3][4]

Discovery

Following the discoveries of two other type II toxin-antitoxin systems,[5][6] the first vapBC system to be characterised was found in Salmonella dublin strain G19 in 1992.[7] 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 12kDa polypeptide, while vagD encoded a smaller 10kDa protein.[7] Their open reading frames were found to overlap by a single nucleotide; suggesting they were translated together, and at a constant molar ratio.[8]

Distribution

VapBC operons have been found in distantly related prokaryotes, including the pathogens Leptospira interrogans,[9] Mycobacterium tuberculosis[10] and Piscirickettsia salmonis.[11] The loci have been described as "surprisingly abundant, especially in Archaea"[12]—vapBC family members made up 37% of all TA families identified by one bioinformatics search[3] and 42% of those found by another.[4]

Bioinformatics searches have discovered vapBC homologues on both chromosomes and plasmids, and often in high copy number per cell. They are less common, however, in firmicutes and cyanobacteria.[3] Genomes with high numbers of vapBC loci include: M. tuberculosis with 45 predicted loci;[10] S.tokodaii with 25;[4] S.solfataricus with 23[4] and Sinorhizobium meliloti with 21.[10]

Function(s)

A proposed consensus secondary structure and primary sequence for the targets of the vapC toxin.[13]

VapC toxins, specifically the PIN domains, act as ribonucleases in cleaving RNA molecules, thereby reducing the rate of translation.[10][14] 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.[15] The specificity of VapC-mediated RNase activity is thought to be influenced by both the primary sequence of the target and secondary structural motifs .[16]

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.[17]

In some organisms, vapBC loci have been assigned other potential functions. In the hyperthermophilic archaean Sulfolobus solfataricus, for example, a vapBC gene cassette is thought to regulate heat shock response.[2]

See also

References

  1. ^ Robson, Jennifer; McKenzie, Joanna L.; Cursons, Ray; Cook, Gregory M.; Arcus, Vickery L. (17 July 2009). "The vapBC Operon from Mycobacterium smegmatis Is An Autoregulated Toxin–Antitoxin Module That Controls Growth via Inhibition of Translation". Journal of Molecular Biology. 390 (3): 353–367. doi:10.1016/j.jmb.2009.05.006. PMID 19445953.
  2. ^ a b Cooper, CR; Daugherty, AJ; Tachdjian, S; Blum, PH; Kelly, RM (Feb 2009). "Role of vapBC toxin-antitoxin loci in the thermal stress response of Sulfolobus solfataricus". Biochemical Society Transactions. 37 (Pt 1): 123–6. doi:10.1042/BST0370123. PMC 2919284. PMID 19143615.
  3. ^ a b c Sevin, Emeric W; Barloy-Hubler, Frédérique (1 January 2007). "RASTA-Bacteria: a web-based tool for identifying toxin-antitoxin loci in prokaryotes". Genome Biology. 8 (8): R155. doi:10.1186/gb-2007-8-8-r155. PMC 2374986. PMID 17678530.
  4. ^ a b c d Pandey, D. P.; Gerdes, K (18 February 2005). "Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes". Nucleic Acids Research. 33 (3): 966–976. doi:10.1093/nar/gki201. PMC 549392. PMID 15718296.
  5. ^ Ogura, T; Hiraga, S (Aug 1983). "Mini-F plasmid genes that couple host cell division to plasmid proliferation". Proceedings of the National Academy of Sciences of the United States of America. 80 (15): 4784–8. doi:10.1073/pnas.80.15.4784. PMC 384129. PMID 6308648.
  6. ^ Bravo, A; de Torrontegui, G; Díaz, R (Nov 1987). "Identification of components of a new stability system of plasmid R1, ParD, that is close to the origin of replication of this plasmid". Molecular & general genetics : MGG. 210 (1): 101–10. doi:10.1007/bf00337764. PMID 3323833.
  7. ^ a b Pullinger, GD; Lax, AJ (Jun 1992). "A Salmonella dublin virulence plasmid locus that affects bacterial growth under nutrient-limited conditions". Molecular Microbiology. 6 (12): 1631–43. doi:10.1111/j.1365-2958.1992.tb00888.x. PMID 1495391.
  8. ^ Das, A; Yanofsky, C (1989-11-25). "Restoration of a translational stop-start overlap reinstates translational coupling in a mutant trpB'-trpA gene pair of the Escherichia coli tryptophan operon". Nucleic Acids Research. 17 (22): 9333–40. doi:10.1093/nar/17.22.9333. PMC 335135. PMID 2685759.
  9. ^ Zhang, YX; Li, J; Guo, XK; Wu, C; Bi, B; Ren, SX; Wu, CF; Zhao, GP (Jun 2004). "Characterization of a novel toxin-antitoxin module, VapBC, encoded by Leptospira interrogans chromosome". Cell Research. 14 (3): 208–16. doi:10.1038/sj.cr.7290221. PMID 15225414.
  10. ^ a b c d Arcus, V. L.; McKenzie, J. L.; Robson, J.; Cook, G. M. (29 October 2010). "The PIN-domain ribonucleases and the prokaryotic VapBC toxin-antitoxin array". Protein Engineering Design and Selection. 24 (1–2): 33–40. doi:10.1093/protein/gzq081. PMID 21036780.
  11. ^ Gómez, FA; Cárdenas, C; Henríquez, V; Marshall, SH (Apr 2011). "Characterization of a functional toxin-antitoxin module in the genome of the fish pathogen Piscirickettsia salmonis". FEMS Microbiology Letters. 317 (1): 83–92. doi:10.1111/j.1574-6968.2011.02218.x. PMID 21241361.
  12. ^ Gerdes, K; Christensen, SK; Løbner-Olesen, A (May 2005). "Prokaryotic toxin-antitoxin stress response loci". Nature Reviews. Microbiology. 3 (5): 371–82. doi:10.1038/nrmicro1147. PMID 15864262.
  13. ^ McKenzie, JL; Robson, J; Berney, M; Smith, TC; Ruthe, A; Gardner, PP; Arcus, VL; Cook, GM (May 2012). "A VapBC toxin-antitoxin module is a posttranscriptional regulator of metabolic flux in mycobacteria". Journal of Bacteriology. 194 (9): 2189–204. doi:10.1128/jb.06790-11. PMC 3347065. PMID 22366418.
  14. ^ Van Melderen, Laurence (1 December 2010). "Toxin–antitoxin systems: why so many, what for?". Current Opinion in Microbiology. 13 (6): 781–785. doi:10.1016/j.mib.2010.10.006. PMID 21041110.
  15. ^ Winther, K. S.; Gerdes, K. (18 April 2011). "Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA". Proceedings of the National Academy of Sciences. 108 (18): 7403–7407. doi:10.1073/pnas.1019587108. PMC 3088637. PMID 21502523.
  16. ^ Sharrock, A.V. (2013) Characterisation of VapBC Toxin-Antitoxins from Mycobacterium tuberculosis. Unpublished Masters Thesis, University of Waikato, Hamilton, New Zealand http://hdl.handle.net/10289/7935
  17. ^ Miallau, L.; Faller, M.; Chiang, J.; Arbing, M.; Guo, F.; Cascio, D.; Eisenberg, D. (4 November 2008). "Structure and Proposed Activity of a Member of the VapBC Family of Toxin-Antitoxin Systems: VapBC-5 from Mycobacterium tuberculosis". Journal of Biological Chemistry. 284 (1): 276–283. doi:10.1074/jbc.M805061200. PMC 2610494. PMID 18952600.

Further reading

External links

This page is based on a wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

Alignments

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Family matches

There is 1 Rfam family which matches this motif.

This section shows the families which have been annotated with this motif. Users should be aware that the motifs are structural constructs and do not necessarily conform to taxonomic boundaries in the way that Rfam families do. More...

Original order Family Accession Family Description Number of Hits Fraction of Hits Sum of Bits Image
3 RF01719 Pseudomon-1/ErsA RNA 2 0.105 28.2 Match Image

References

This section shows the database cross-references that we have for this Rfam motif.

Literature references

  1. McKenzie JL, Robson J, Berney M, Smith TC, Ruthe A, Gardner PP, Arcus VL, Cook GM J Bacteriol. 2012 A VapBC Toxin-Antitoxin Module is a Post-Transcriptional Regulator of Metabolic Flux in Mycobacteria. PUBMED:22366418

External database links

Curation and motif details

This section shows the detailed information about the Rfam motif. We're happy to receive updated or improved alignments for new or existing families. Submit your new alignment and we'll take a look.

Curation

Seed source Published; PMID:22366418
Structure source N/A
Type Internal Loop
Author Gardner PP
Alignment details
Alignment Number of
sequences
Average length Sequence
identity (%)
seed 38 53.71 41

Model information

Build commands
cmbuild -F CM SEED
cmcalibrate --mpi --seed 1 CM
Gathering cutoff 13.0
Covariance model Download the Infernal CM for the motif here