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[[Image:3nfc.jpg|left|200px]]
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{{STRUCTURE_3nfc|  PDB=3nfc  |  SCENE=  }}  
{{STRUCTURE_3nfc|  PDB=3nfc  |  SCENE=  }}  
===Crystal structure of E.coli MazF Toxin===
===Crystal structure of E.coli MazF Toxin===


==Function==
[[http://www.uniprot.org/uniprot/CHPA_ECOLI CHPA_ECOLI]] Toxic component of a toxin-antitoxin (TA) module. MazF is a sequence-specific mRNA endoribonuclease that inhibits protein synthesis and induces bacterial stasis. It is very stable, single-strand specific and cleavage is independent of the ribosome, although translation enhances cleavage for some mRNAs. Cleavage usually occurs between the first A and C of ACA sequences, yielding a 2',3'-cyclic phosphate and a free 5'-OH. The endoribonuclease activity (a toxin) is inhibited by the labile cognate antitoxin MazE. Toxicity results when the levels of MazE decrease in the cell, leading to mRNA degradation. This effect can be rescued by expression of MazE, but after 6 hours in rich medium overexpression of MazF leads to programmed cell death. MazF-mediated cell death occurs following a number of stress conditions in a relA-dependent fashion and only when cells are in log phase. Cell growth and viability are not affected when MazF and MazE are coexpressed. Programmed cell death occurs when cells are at high density and depends on the presence of MazEF and a quorum sensing pentapeptide, the extracellular death factor (EDF) with sequence NNWNN, probably produced from the zwg gene product glucose-6-phosphate 1-dehydrogenase. Both MazE and MazEF bind to the promoter region of the mazEF operon to inhibit their transcription.<ref>PMID:8650219</ref> <ref>PMID:12123459</ref> <ref>PMID:15150257</ref> <ref>PMID:15576778</ref> <ref>PMID:15316771</ref> <ref>PMID:15537630</ref> <ref>PMID:19707553</ref>  Might also serve to protect cells against bacteriophage; in the presence of MazEF fewer P1 phage are produced than in a disruption strain. For strain K38 most wild-type cells are killed by not by phage lysis; it was suggested that MazEF causes P1 phage exclusion from the bacterial population. This phenomenon is strain dependent.<ref>PMID:8650219</ref> <ref>PMID:12123459</ref> <ref>PMID:15150257</ref> <ref>PMID:15576778</ref> <ref>PMID:15316771</ref> <ref>PMID:15537630</ref> <ref>PMID:19707553</ref>  Cell death governed by the mazEF and dinJ-yafQ TA modules seems to play a role in biofilm formation, while mazEF is also implicated in cell death in liquid media.<ref>PMID:8650219</ref> <ref>PMID:12123459</ref> <ref>PMID:15150257</ref> <ref>PMID:15576778</ref> <ref>PMID:15316771</ref> <ref>PMID:15537630</ref> <ref>PMID:19707553</ref> 


==About this Structure==
==About this Structure==
[[3nfc]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NFC OCA].  
[[3nfc]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NFC OCA].  
==Reference==
<references group="xtra"/><references/>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Su, X.]]
[[Category: Su, X.]]

Revision as of 14:40, 24 April 2013

Template:STRUCTURE 3nfc

Crystal structure of E.coli MazF ToxinCrystal structure of E.coli MazF Toxin

FunctionFunction

[CHPA_ECOLI] Toxic component of a toxin-antitoxin (TA) module. MazF is a sequence-specific mRNA endoribonuclease that inhibits protein synthesis and induces bacterial stasis. It is very stable, single-strand specific and cleavage is independent of the ribosome, although translation enhances cleavage for some mRNAs. Cleavage usually occurs between the first A and C of ACA sequences, yielding a 2',3'-cyclic phosphate and a free 5'-OH. The endoribonuclease activity (a toxin) is inhibited by the labile cognate antitoxin MazE. Toxicity results when the levels of MazE decrease in the cell, leading to mRNA degradation. This effect can be rescued by expression of MazE, but after 6 hours in rich medium overexpression of MazF leads to programmed cell death. MazF-mediated cell death occurs following a number of stress conditions in a relA-dependent fashion and only when cells are in log phase. Cell growth and viability are not affected when MazF and MazE are coexpressed. Programmed cell death occurs when cells are at high density and depends on the presence of MazEF and a quorum sensing pentapeptide, the extracellular death factor (EDF) with sequence NNWNN, probably produced from the zwg gene product glucose-6-phosphate 1-dehydrogenase. Both MazE and MazEF bind to the promoter region of the mazEF operon to inhibit their transcription.[1] [2] [3] [4] [5] [6] [7] Might also serve to protect cells against bacteriophage; in the presence of MazEF fewer P1 phage are produced than in a disruption strain. For strain K38 most wild-type cells are killed by not by phage lysis; it was suggested that MazEF causes P1 phage exclusion from the bacterial population. This phenomenon is strain dependent.[8] [9] [10] [11] [12] [13] [14] Cell death governed by the mazEF and dinJ-yafQ TA modules seems to play a role in biofilm formation, while mazEF is also implicated in cell death in liquid media.[15] [16] [17] [18] [19] [20] [21]

About this StructureAbout this Structure

3nfc is a 6 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

  1. Aizenman E, Engelberg-Kulka H, Glaser G. An Escherichia coli chromosomal "addiction module" regulated by guanosine [corrected] 3',5'-bispyrophosphate: a model for programmed bacterial cell death. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6059-63. PMID:8650219
  2. Pedersen K, Christensen SK, Gerdes K. Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol Microbiol. 2002 Jul;45(2):501-10. PMID:12123459
  3. Hazan R, Sat B, Engelberg-Kulka H. Escherichia coli mazEF-mediated cell death is triggered by various stressful conditions. J Bacteriol. 2004 Jun;186(11):3663-9. PMID:15150257 doi:10.1128/JB.186.11.3663-3669.2004
  4. Amitai S, Yassin Y, Engelberg-Kulka H. MazF-mediated cell death in Escherichia coli: a point of no return. J Bacteriol. 2004 Dec;186(24):8295-300. PMID:15576778 doi:10.1128/JB.186.24.8295-8300.2004
  5. Hazan R, Engelberg-Kulka H. Escherichia coli mazEF-mediated cell death as a defense mechanism that inhibits the spread of phage P1. Mol Genet Genomics. 2004 Sep;272(2):227-34. Epub 2004 Aug 14. PMID:15316771 doi:10.1007/s00438-004-1048-y
  6. Zhang Y, Zhang J, Hara H, Kato I, Inouye M. Insights into the mRNA cleavage mechanism by MazF, an mRNA interferase. J Biol Chem. 2005 Feb 4;280(5):3143-50. Epub 2004 Nov 10. PMID:15537630 doi:10.1074/jbc.M411811200
  7. Kolodkin-Gal I, Verdiger R, Shlosberg-Fedida A, Engelberg-Kulka H. A differential effect of E. coli toxin-antitoxin systems on cell death in liquid media and biofilm formation. PLoS One. 2009 Aug 26;4(8):e6785. doi: 10.1371/journal.pone.0006785. PMID:19707553 doi:10.1371/journal.pone.0006785
  8. Aizenman E, Engelberg-Kulka H, Glaser G. An Escherichia coli chromosomal "addiction module" regulated by guanosine [corrected] 3',5'-bispyrophosphate: a model for programmed bacterial cell death. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6059-63. PMID:8650219
  9. Pedersen K, Christensen SK, Gerdes K. Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol Microbiol. 2002 Jul;45(2):501-10. PMID:12123459
  10. Hazan R, Sat B, Engelberg-Kulka H. Escherichia coli mazEF-mediated cell death is triggered by various stressful conditions. J Bacteriol. 2004 Jun;186(11):3663-9. PMID:15150257 doi:10.1128/JB.186.11.3663-3669.2004
  11. Amitai S, Yassin Y, Engelberg-Kulka H. MazF-mediated cell death in Escherichia coli: a point of no return. J Bacteriol. 2004 Dec;186(24):8295-300. PMID:15576778 doi:10.1128/JB.186.24.8295-8300.2004
  12. Hazan R, Engelberg-Kulka H. Escherichia coli mazEF-mediated cell death as a defense mechanism that inhibits the spread of phage P1. Mol Genet Genomics. 2004 Sep;272(2):227-34. Epub 2004 Aug 14. PMID:15316771 doi:10.1007/s00438-004-1048-y
  13. Zhang Y, Zhang J, Hara H, Kato I, Inouye M. Insights into the mRNA cleavage mechanism by MazF, an mRNA interferase. J Biol Chem. 2005 Feb 4;280(5):3143-50. Epub 2004 Nov 10. PMID:15537630 doi:10.1074/jbc.M411811200
  14. Kolodkin-Gal I, Verdiger R, Shlosberg-Fedida A, Engelberg-Kulka H. A differential effect of E. coli toxin-antitoxin systems on cell death in liquid media and biofilm formation. PLoS One. 2009 Aug 26;4(8):e6785. doi: 10.1371/journal.pone.0006785. PMID:19707553 doi:10.1371/journal.pone.0006785
  15. Aizenman E, Engelberg-Kulka H, Glaser G. An Escherichia coli chromosomal "addiction module" regulated by guanosine [corrected] 3',5'-bispyrophosphate: a model for programmed bacterial cell death. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6059-63. PMID:8650219
  16. Pedersen K, Christensen SK, Gerdes K. Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol Microbiol. 2002 Jul;45(2):501-10. PMID:12123459
  17. Hazan R, Sat B, Engelberg-Kulka H. Escherichia coli mazEF-mediated cell death is triggered by various stressful conditions. J Bacteriol. 2004 Jun;186(11):3663-9. PMID:15150257 doi:10.1128/JB.186.11.3663-3669.2004
  18. Amitai S, Yassin Y, Engelberg-Kulka H. MazF-mediated cell death in Escherichia coli: a point of no return. J Bacteriol. 2004 Dec;186(24):8295-300. PMID:15576778 doi:10.1128/JB.186.24.8295-8300.2004
  19. Hazan R, Engelberg-Kulka H. Escherichia coli mazEF-mediated cell death as a defense mechanism that inhibits the spread of phage P1. Mol Genet Genomics. 2004 Sep;272(2):227-34. Epub 2004 Aug 14. PMID:15316771 doi:10.1007/s00438-004-1048-y
  20. Zhang Y, Zhang J, Hara H, Kato I, Inouye M. Insights into the mRNA cleavage mechanism by MazF, an mRNA interferase. J Biol Chem. 2005 Feb 4;280(5):3143-50. Epub 2004 Nov 10. PMID:15537630 doi:10.1074/jbc.M411811200
  21. Kolodkin-Gal I, Verdiger R, Shlosberg-Fedida A, Engelberg-Kulka H. A differential effect of E. coli toxin-antitoxin systems on cell death in liquid media and biofilm formation. PLoS One. 2009 Aug 26;4(8):e6785. doi: 10.1371/journal.pone.0006785. PMID:19707553 doi:10.1371/journal.pone.0006785

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