1ub4: Difference between revisions

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<StructureSection load='1ub4' size='340' side='right'caption='[[1ub4]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
<StructureSection load='1ub4' size='340' side='right'caption='[[1ub4]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1ub4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UB4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1UB4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1ub4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UB4 FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mazF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895]), MazE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1ub4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ub4 OCA], [http://pdbe.org/1ub4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ub4 RCSB], [http://www.ebi.ac.uk/pdbsum/1ub4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ub4 ProSAT], [http://www.topsan.org/Proteins/NYSGXRC/1ub4 TOPSAN]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ub4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ub4 OCA], [https://pdbe.org/1ub4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ub4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ub4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ub4 ProSAT], [https://www.topsan.org/Proteins/NYSGXRC/1ub4 TOPSAN]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/MAZF_ECOLI MAZF_ECOLI]] Toxic component of a type II toxin-antitoxin (TA) module. A sequence-specific endoribonuclease it inhibits protein synthesis by cleaving mRNA and inducing bacterial stasis. It is stable, single-strand specific with mRNA cleavage independent of the ribosome, although translation enhances cleavage for some mRNAs (PubMed:18854355). Cleavage occurs at the 5'-end of ACA sequences, yielding a 2',3'-cyclic phosphate and a free 5'-OH, although cleavage can also occur on the 3'-end of the first A (PubMed:15537630, PubMed:23280569). Digests 16S rRNA in vivo 43 nts upstream of the C-terminus; this removes the anti-Shine-Dalgarno sequence forming a mixed population of wild-type and "stress ribosomes". Stress ribosomes do not translate leader-containing mRNA but are proficient in translation of leaderless mRNA, which alters the protein expression profile of the cell; MazF produces some leaderless mRNA (PubMed:21944167). The toxic endoribonuclease activity is inhibited by its 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 (PubMed:8650219, PubMed:11222603). MazF-mediated cell death occurs following a number of stress conditions in a relA-dependent fashion and only when cells are in log phase; sigma factor S (rpoS) protects stationary phase cells from MazF-killing (PubMed:15150257, PubMed:19251848). Cell growth and viability are not affected when MazF and MazE are coexpressed. Both MazE and MazE-MazF bind to the promoter region of the mazE-mazF operon to inhibit their own transcription. MazE has higher affinity for promoter DNA in the presence of MazF (PubMed:25564525). Cross-talk can occur between different TA modules. Ectopic expression of this toxin induces transcription of the relBEF TA module operon with specific cleavage of the mRNA produced (PubMed:23432955).<ref>PMID:11071896</ref> <ref>PMID:11222603</ref> <ref>PMID:15150257</ref> <ref>PMID:15537630</ref> <ref>PMID:18854355</ref> <ref>PMID:19251848</ref> <ref>PMID:21944167</ref> <ref>PMID:23280569</ref> <ref>PMID:23432955</ref> <ref>PMID:25564525</ref> <ref>PMID:8650219</ref>  Might also serve to protect cells against bacteriophage; in the presence of MazE-MazF fewer P1 phage are produced than in a disrupted strain. For strain K38 most wild-type cells are killed but not by phage lysis; it was suggested that MazE-MazF causes P1 phage exclusion from the bacterial population. This phenomenon is strain dependent.<ref>PMID:15316771</ref>  The physiological role of this TA module is debated. Programmed cell death (PCD) occurs when cells are at high density and depends on the presence of MazE-MazF and a quorum sensing pentapeptide, the extracellular death factor (EDF) with sequence Asn-Asn-Trp-Asn-Asn (NNWNN), probably produced from the zwf gene product glucose-6-phosphate 1-dehydrogenase (PubMed:17962566, PubMed:18310334). Cell death governed by the MazE-MazF and DinJ-YafQ TA modules seems to play a role in biofilm formation, while MazE-MazF is also implicated in cell death in liquid media (PubMed:19707553). Implicated in hydroxy radical-mediated cell death induced by hydroxyurea treatment (PubMed:20005847, PubMed:23416055). In conjunction with EDF prevents apoptotic-like death (ALD) in the presence of DNA damaging agents, probably by reducing recA mRNA levels in a non-endonuclease-mediated manner (PubMed:22412352). Other studies (in strains BW25113 and MC4100, the latter makes EDF) demonstrate MazF does not cause PCD but instead bacteriostasis and possibly a dormant state as well as persister cell generation (PubMed:24375411).<ref>PMID:17962566</ref> <ref>PMID:18310334</ref> <ref>PMID:19707553</ref> <ref>PMID:20005847</ref> <ref>PMID:21419338</ref> <ref>PMID:22412352</ref> <ref>PMID:23416055</ref> <ref>PMID:24375411</ref> <ref>PMID:8650219</ref> [[http://www.uniprot.org/uniprot/MAZE_ECOLI MAZE_ECOLI]] Antitoxin component of a toxin-antitoxin (TA) module. Labile antitoxin that binds to the MazF mRNA interferase toxin and neutralizes its endoribonuclease activity. Is considered to be an 'addiction' molecule as the cell will die in its absence. The endoribonuclease activity (MazF, 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 the overexpression of MazF leads to programmed cell death. Cell growth and viability are not affected when MazF and MazE are coexpressed. Both MazE and MazE-MazF bind to the promoter region of the mazE-mazF operon to inhibit their transcription.  Cell death governed by the MazE-MazF and DinJ-YafQ TA modules seems to play a role in biofilm formation, while MazE-MazF is also implicated in cell death in liquid media.
[https://www.uniprot.org/uniprot/MAZF_ECOLI MAZF_ECOLI] Toxic component of a type II toxin-antitoxin (TA) module. A sequence-specific endoribonuclease it inhibits protein synthesis by cleaving mRNA and inducing bacterial stasis. It is stable, single-strand specific with mRNA cleavage independent of the ribosome, although translation enhances cleavage for some mRNAs (PubMed:18854355). Cleavage occurs at the 5'-end of ACA sequences, yielding a 2',3'-cyclic phosphate and a free 5'-OH, although cleavage can also occur on the 3'-end of the first A (PubMed:15537630, PubMed:23280569). Digests 16S rRNA in vivo 43 nts upstream of the C-terminus; this removes the anti-Shine-Dalgarno sequence forming a mixed population of wild-type and "stress ribosomes". Stress ribosomes do not translate leader-containing mRNA but are proficient in translation of leaderless mRNA, which alters the protein expression profile of the cell; MazF produces some leaderless mRNA (PubMed:21944167). The toxic endoribonuclease activity is inhibited by its 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 (PubMed:8650219, PubMed:11222603). MazF-mediated cell death occurs following a number of stress conditions in a relA-dependent fashion and only when cells are in log phase; sigma factor S (rpoS) protects stationary phase cells from MazF-killing (PubMed:15150257, PubMed:19251848). Cell growth and viability are not affected when MazF and MazE are coexpressed. Both MazE and MazE-MazF bind to the promoter region of the mazE-mazF operon to inhibit their own transcription. MazE has higher affinity for promoter DNA in the presence of MazF (PubMed:25564525). Cross-talk can occur between different TA modules. Ectopic expression of this toxin induces transcription of the relBEF TA module operon with specific cleavage of the mRNA produced (PubMed:23432955).<ref>PMID:11071896</ref> <ref>PMID:11222603</ref> <ref>PMID:15150257</ref> <ref>PMID:15537630</ref> <ref>PMID:18854355</ref> <ref>PMID:19251848</ref> <ref>PMID:21944167</ref> <ref>PMID:23280569</ref> <ref>PMID:23432955</ref> <ref>PMID:25564525</ref> <ref>PMID:8650219</ref>  Might also serve to protect cells against bacteriophage; in the presence of MazE-MazF fewer P1 phage are produced than in a disrupted strain. For strain K38 most wild-type cells are killed but not by phage lysis; it was suggested that MazE-MazF causes P1 phage exclusion from the bacterial population. This phenomenon is strain dependent.<ref>PMID:15316771</ref>  The physiological role of this TA module is debated. Programmed cell death (PCD) occurs when cells are at high density and depends on the presence of MazE-MazF and a quorum sensing pentapeptide, the extracellular death factor (EDF) with sequence Asn-Asn-Trp-Asn-Asn (NNWNN), probably produced from the zwf gene product glucose-6-phosphate 1-dehydrogenase (PubMed:17962566, PubMed:18310334). Cell death governed by the MazE-MazF and DinJ-YafQ TA modules seems to play a role in biofilm formation, while MazE-MazF is also implicated in cell death in liquid media (PubMed:19707553). Implicated in hydroxy radical-mediated cell death induced by hydroxyurea treatment (PubMed:20005847, PubMed:23416055). In conjunction with EDF prevents apoptotic-like death (ALD) in the presence of DNA damaging agents, probably by reducing recA mRNA levels in a non-endonuclease-mediated manner (PubMed:22412352). Other studies (in strains BW25113 and MC4100, the latter makes EDF) demonstrate MazF does not cause PCD but instead bacteriostasis and possibly a dormant state as well as persister cell generation (PubMed:24375411).<ref>PMID:17962566</ref> <ref>PMID:18310334</ref> <ref>PMID:19707553</ref> <ref>PMID:20005847</ref> <ref>PMID:21419338</ref> <ref>PMID:22412352</ref> <ref>PMID:23416055</ref> <ref>PMID:24375411</ref> <ref>PMID:8650219</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bacillus coli migula 1895]]
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Burley, S K]]
[[Category: Burley SK]]
[[Category: Hanaoka, F]]
[[Category: Hanaoka F]]
[[Category: Kamada, K]]
[[Category: Kamada K]]
[[Category: Structural genomic]]
[[Category: Addiction module]]
[[Category: Antidote]]
[[Category: Dna binding protein]]
[[Category: NYSGXRC, New York SGX Research Center for Structural Genomics]]
[[Category: Post-segregation]]
[[Category: Programmed cell death]]
[[Category: PSI, Protein structure initiative]]
[[Category: Toxin]]

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