| Structural highlights
Function
[YEFM_ECOLI] Antitoxin component of a toxin-antitoxin (TA) module. Antitoxin that counteracts the effect of the YoeB toxin. YefM binds to the promoter region of the yefM-yeoB operon to repress transcription, YeoB acts as a corepressor.[1] [2] [3] [4] [YOEB_ECOLI] Toxic component of a toxin-antitoxin (TA) module. Its mode of function is controversial; it has been proposed to be an mRNA interferase but also an inhibitor of translation initiation. When overproduced in wild-type cells, inhibits bacterial growth and translation by cleavage of mRNA molecules while it has a weak effect on colony forming ability. Overproduction of Lon protease specifically activates YoeB-dependent mRNA cleavage, leading to lethality. YefM binds to the promoter region of the yefM-yeoB operon to repress transcription, YeoB acts as a corepressor.[5] [6] [7] [8] [9] [10] [11] [12] Shown in vitro to be an mRNA interferase that requires translation for substrate cleavage; if the mRNA is mutated so as to not be translatable it is no longer cleaved. Cleavage only occurs within translated regions. Has RNase activity and preferentially cleaves at the 3'-end of purine ribonucleotides.[13] [14] [15] [16] [17] [18] [19] [20] Also shown in vitro to be a translation initiation blocker. Binds to the 70S ribosome and 50S ribosomal subunit; binding is inhibited by hygromycin A and tetracycline, both of which bind to the 30S subunit in the A site. Thus YoeB is located at the interface between 50S and 30S ribosomes and interacts with the A site where it cleaves mRNA, blocking translation initiation.[21] [22] [23] [24] [25] [26] [27] [28]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The eubacterial chromosome encodes various addiction modules that control global levels of translation through RNA degradation. Crystal structures of the Escherichia coli YefM2 (antitoxin)-YoeB (toxin) complex and the free YoeB toxin have been determined. The structure of the heterotrimeric complex reveals an asymmetric disorder-to-order recognition strategy, in which one C terminus of the YefM homodimer exclusively interacts with an atypical microbial ribonuclease (RNase) fold of YoeB. Comparison with the YefM-free YoeB structure indicates a conformational rearrangement of the RNase catalytic site of YoeB, induced by interaction with YefM. Complementary biochemical experiments demonstrate that the YoeB toxin has an in vitro RNase activity that preferentially cleaves at the 3' end of purine ribonucleotides.
Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin.,Kamada K, Hanaoka F Mol Cell. 2005 Aug 19;19(4):497-509. PMID:16109374[29]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cherny I, Gazit E. The YefM antitoxin defines a family of natively unfolded proteins: implications as a novel antibacterial target. J Biol Chem. 2004 Feb 27;279(9):8252-61. Epub 2003 Dec 14. PMID:14672926 doi:http://dx.doi.org/10.1074/jbc.M308263200
- ↑ Christensen SK, Maenhaut-Michel G, Mine N, Gottesman S, Gerdes K, Van Melderen L. Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: involvement of the yefM-yoeB toxin-antitoxin system. Mol Microbiol. 2004 Mar;51(6):1705-17. PMID:15009896
- ↑ Kedzierska B, Lian LY, Hayes F. Toxin-antitoxin regulation: bimodal interaction of YefM-YoeB with paired DNA palindromes exerts transcriptional autorepression. Nucleic Acids Res. 2007;35(1):325-39. Epub 2006 Dec 14. PMID:17170003 doi:http://dx.doi.org/10.1093/nar/gkl1028
- ↑ Bailey SE, Hayes F. Influence of operator site geometry on transcriptional control by the YefM-YoeB toxin-antitoxin complex. J Bacteriol. 2009 Feb;191(3):762-72. doi: 10.1128/JB.01331-08. Epub 2008 Nov 21. PMID:19028895 doi:http://dx.doi.org/10.1128/JB.01331-08
- ↑ Cherny I, Gazit E. The YefM antitoxin defines a family of natively unfolded proteins: implications as a novel antibacterial target. J Biol Chem. 2004 Feb 27;279(9):8252-61. Epub 2003 Dec 14. PMID:14672926 doi:http://dx.doi.org/10.1074/jbc.M308263200
- ↑ Christensen SK, Maenhaut-Michel G, Mine N, Gottesman S, Gerdes K, Van Melderen L. Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: involvement of the yefM-yoeB toxin-antitoxin system. Mol Microbiol. 2004 Mar;51(6):1705-17. PMID:15009896
- ↑ Kedzierska B, Lian LY, Hayes F. Toxin-antitoxin regulation: bimodal interaction of YefM-YoeB with paired DNA palindromes exerts transcriptional autorepression. Nucleic Acids Res. 2007;35(1):325-39. Epub 2006 Dec 14. PMID:17170003 doi:http://dx.doi.org/10.1093/nar/gkl1028
- ↑ Christensen-Dalsgaard M, Gerdes K. Translation affects YoeB and MazF messenger RNA interferase activities by different mechanisms. Nucleic Acids Res. 2008 Nov;36(20):6472-81. doi: 10.1093/nar/gkn667. Epub 2008, Oct 14. PMID:18854355 doi:http://dx.doi.org/10.1093/nar/gkn667
- ↑ Bailey SE, Hayes F. Influence of operator site geometry on transcriptional control by the YefM-YoeB toxin-antitoxin complex. J Bacteriol. 2009 Feb;191(3):762-72. doi: 10.1128/JB.01331-08. Epub 2008 Nov 21. PMID:19028895 doi:http://dx.doi.org/10.1128/JB.01331-08
- ↑ Zhang Y, Inouye M. The inhibitory mechanism of protein synthesis by YoeB, an Escherichia coli toxin. J Biol Chem. 2009 Mar 13;284(11):6627-38. doi: 10.1074/jbc.M808779200. Epub 2009 , Jan 5. PMID:19124462 doi:http://dx.doi.org/10.1074/jbc.M808779200
- ↑ Winther KS, Gerdes K. Ectopic production of VapCs from Enterobacteria inhibits translation and trans-activates YoeB mRNA interferase. Mol Microbiol. 2009 May;72(4):918-30. doi: 10.1111/j.1365-2958.2009.06694.x. Epub, 2009 Apr 14. PMID:19400780 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.06694.x
- ↑ Kamada K, Hanaoka F. Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin. Mol Cell. 2005 Aug 19;19(4):497-509. PMID:16109374 doi:10.1016/j.molcel.2005.07.004
- ↑ Cherny I, Gazit E. The YefM antitoxin defines a family of natively unfolded proteins: implications as a novel antibacterial target. J Biol Chem. 2004 Feb 27;279(9):8252-61. Epub 2003 Dec 14. PMID:14672926 doi:http://dx.doi.org/10.1074/jbc.M308263200
- ↑ Christensen SK, Maenhaut-Michel G, Mine N, Gottesman S, Gerdes K, Van Melderen L. Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: involvement of the yefM-yoeB toxin-antitoxin system. Mol Microbiol. 2004 Mar;51(6):1705-17. PMID:15009896
- ↑ Kedzierska B, Lian LY, Hayes F. Toxin-antitoxin regulation: bimodal interaction of YefM-YoeB with paired DNA palindromes exerts transcriptional autorepression. Nucleic Acids Res. 2007;35(1):325-39. Epub 2006 Dec 14. PMID:17170003 doi:http://dx.doi.org/10.1093/nar/gkl1028
- ↑ Christensen-Dalsgaard M, Gerdes K. Translation affects YoeB and MazF messenger RNA interferase activities by different mechanisms. Nucleic Acids Res. 2008 Nov;36(20):6472-81. doi: 10.1093/nar/gkn667. Epub 2008, Oct 14. PMID:18854355 doi:http://dx.doi.org/10.1093/nar/gkn667
- ↑ Bailey SE, Hayes F. Influence of operator site geometry on transcriptional control by the YefM-YoeB toxin-antitoxin complex. J Bacteriol. 2009 Feb;191(3):762-72. doi: 10.1128/JB.01331-08. Epub 2008 Nov 21. PMID:19028895 doi:http://dx.doi.org/10.1128/JB.01331-08
- ↑ Zhang Y, Inouye M. The inhibitory mechanism of protein synthesis by YoeB, an Escherichia coli toxin. J Biol Chem. 2009 Mar 13;284(11):6627-38. doi: 10.1074/jbc.M808779200. Epub 2009 , Jan 5. PMID:19124462 doi:http://dx.doi.org/10.1074/jbc.M808779200
- ↑ Winther KS, Gerdes K. Ectopic production of VapCs from Enterobacteria inhibits translation and trans-activates YoeB mRNA interferase. Mol Microbiol. 2009 May;72(4):918-30. doi: 10.1111/j.1365-2958.2009.06694.x. Epub, 2009 Apr 14. PMID:19400780 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.06694.x
- ↑ Kamada K, Hanaoka F. Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin. Mol Cell. 2005 Aug 19;19(4):497-509. PMID:16109374 doi:10.1016/j.molcel.2005.07.004
- ↑ Cherny I, Gazit E. The YefM antitoxin defines a family of natively unfolded proteins: implications as a novel antibacterial target. J Biol Chem. 2004 Feb 27;279(9):8252-61. Epub 2003 Dec 14. PMID:14672926 doi:http://dx.doi.org/10.1074/jbc.M308263200
- ↑ Christensen SK, Maenhaut-Michel G, Mine N, Gottesman S, Gerdes K, Van Melderen L. Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: involvement of the yefM-yoeB toxin-antitoxin system. Mol Microbiol. 2004 Mar;51(6):1705-17. PMID:15009896
- ↑ Kedzierska B, Lian LY, Hayes F. Toxin-antitoxin regulation: bimodal interaction of YefM-YoeB with paired DNA palindromes exerts transcriptional autorepression. Nucleic Acids Res. 2007;35(1):325-39. Epub 2006 Dec 14. PMID:17170003 doi:http://dx.doi.org/10.1093/nar/gkl1028
- ↑ Christensen-Dalsgaard M, Gerdes K. Translation affects YoeB and MazF messenger RNA interferase activities by different mechanisms. Nucleic Acids Res. 2008 Nov;36(20):6472-81. doi: 10.1093/nar/gkn667. Epub 2008, Oct 14. PMID:18854355 doi:http://dx.doi.org/10.1093/nar/gkn667
- ↑ Bailey SE, Hayes F. Influence of operator site geometry on transcriptional control by the YefM-YoeB toxin-antitoxin complex. J Bacteriol. 2009 Feb;191(3):762-72. doi: 10.1128/JB.01331-08. Epub 2008 Nov 21. PMID:19028895 doi:http://dx.doi.org/10.1128/JB.01331-08
- ↑ Zhang Y, Inouye M. The inhibitory mechanism of protein synthesis by YoeB, an Escherichia coli toxin. J Biol Chem. 2009 Mar 13;284(11):6627-38. doi: 10.1074/jbc.M808779200. Epub 2009 , Jan 5. PMID:19124462 doi:http://dx.doi.org/10.1074/jbc.M808779200
- ↑ Winther KS, Gerdes K. Ectopic production of VapCs from Enterobacteria inhibits translation and trans-activates YoeB mRNA interferase. Mol Microbiol. 2009 May;72(4):918-30. doi: 10.1111/j.1365-2958.2009.06694.x. Epub, 2009 Apr 14. PMID:19400780 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.06694.x
- ↑ Kamada K, Hanaoka F. Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin. Mol Cell. 2005 Aug 19;19(4):497-509. PMID:16109374 doi:10.1016/j.molcel.2005.07.004
- ↑ Kamada K, Hanaoka F. Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin. Mol Cell. 2005 Aug 19;19(4):497-509. PMID:16109374 doi:10.1016/j.molcel.2005.07.004
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