Species: Escherichia coli K-12 substr. MG1655
Subunit composition of
YefM-YoeB antitoxin/toxin complex and DNA-binding transcriptional repressor = [YoeB][YefM]2
toxin of the YoeB-YefM toxin-antitoxin pair = YoeB (extended summary available)
YefM antitoxin of the YoeB-YefM toxin-antitoxin pair and DNA binding transcriptional repressor = YefM
YefM is a transcriptional DNA-binding autorepressor for the yefM-yoeB operon. In addition, YefM also functions as an antitoxin to form a complex with YoeB, which is a toxin that is counteracted by YefM antitoxin [Kedzierska07]. YefM can bind alone with low affinity to the yefM-yoeB operator, but together with YoeB it has an enhanced DNA-binding affinity compared to free YefM [Kedzierska07]. YoeB enhances the interaction with YefM by affecting the YefM conformation to one that is more favorable for DNA binding and/or by stabilizing the nucleoprotein complex at the operator site and reducing basal expression of the yefM-yoeB operon [Kedzierska07, Bailey09].
The yefM gene is upregulated during growth in biofilms [Ren04a] and yefM-yoeB is upregulated in persister cells [Shah06]; it is probable that derepression of yefM-yoeB autoregulation occurs in these circumstances in response to an as-yet-unknown environmental or cell cycle signal(s) that interferes with the YefM-YoeB-operator interaction [Bailey09].
The operator site 5' of yefM-yoeB comprises adjacent long (L) and short (S) palindromes with core 5'-TGTACA-3' motifs with a center-to-center distance of 12 bp [Kedzierska07], which was suggested to be crucial for the correct stable positioning of YefM-YoeB at the two repeats [Bailey09]. This sequence organization is common in yefM-yoeB regulatory regions in diverse genomes, suggesting that interaction of YefM-YoeB with these motifs is a conserved mechanism of operon autoregulation [Kedzierska07].
Nevertheless, YefM originally was described as a native unstructured protein [Cherny04]; later it was reevaluated as experimental, and modeling data have demonstrated that the protein is at least partially folded [Kedzierska07, Pomerantsev01] and dimeric [Kedzierska07].
The YefM antitoxin forms a heterotrimeric complex with the YoeB toxin (YefM2-YoeB) [Cherny05, Kamada05]. The tertiary structure of the YoeB toxin and the YefM2-YoeB complex has been described [Kamada05]. In the complex, one C terminus in the YefM homodimer is unfolded and the other one shows an α-helical conformation and conceals the endoribonuclease fold of YoeB. Two N-terminal segments of YefM form a symmetrical dimer within the YefM2-YoeB heterotrimeric complex and do not contact YoeB directly [Bailey09].
YefM does not possess a canonical DNA-binding motif, but instead a pair of basic residues, R10 and R31, conserved in many YefM homologs are absolutely necessary for DNA binding by the YefM-YoeB complex [Grady03, Bailey09, Kamada05].
Molecular Weight: 30.0 kD (experimental) [Kamada05]
DNA binding site length: 14 base-pairs
Symmetry: Inverted Repeat
Consensus DNA Binding Sequence: TCATTGTACAATGA
|Gene:||yoeB||Accession Numbers: G0-9121 (MetaCyc), b4539, ECK2011|
Sequence Length: 84 AAs
Molecular Weight: 10.216 kD (from nucleotide sequence)
|MultiFun Terms:||cell processes → defense/survival|
YoeB is the toxin of the YoeB-YefM toxin-antitoxin pair [Grady03, Cherny04]. The YoeB toxin induces cleavage of translated mRNAs. YoeB can be activated by overproduction of the Lon protease (which is lethal), suggesting that Lon degrades YefM [Christensen04]. YoeB inhibits translation initiation by interacting with the A site of the ribosome [Zhang09a], leading to mRNA cleavage after the second position in the A-site codon and producing a 3'-phosphate product [Feng13].
Earlier experiments showed that YoeB is an endoribonuclease that preferentially cleaves at the 3' end of purine ribonucleotides [Kamada05]. The activity is dependent on mRNA translation in vivo, and the cleavage pattern is determined by the reading frame [ChristensenDals08].
YoeB recognizes and binds to an unstructured peptide sequence within YefM [Cherny04]. The YoeB-YefM complex was initially reported to have a stoichiometry of YoeB2-YefM1 [Cherny05]. However, crystal structures show a YoeB1-YefM2 complex where interaction with YefM induces a conformational change in the YoeB RNase catalytic site [Kamada05]. YoeB enhances the transcription repressor activity of YefM [Kedzierska07].
A crystal structure of YoeB bound to a 70S ribosome has been solved. A YoeB dimer was found to bind to the ribosomal A site [Feng13].
yefM-yoeB is overexpressed in a selected cell population that resembles persister cells [Shah06]. Deletion of yoeB increases biofilm formation [Kim09a]. Overexpression of YoeB causes loss of cell viability approximately 2 hours after induction [KolodkinGal09].
|Gene:||yefM||Accession Numbers: EG12844 (MetaCyc), b2017, ECK2012|
Sequence Length: 83 AAs
Molecular Weight: 9.308 kD (from nucleotide sequence)
|MultiFun Terms:||cell processes → defense/survival|
Cherny05: Cherny I, Rockah L, Gazit E (2005). "The YoeB toxin is a folded protein that forms a physical complex with the unfolded YefM antitoxin. Implications for a structural-based differential stability of toxin-antitoxin systems." J Biol Chem 280(34);30063-72. PMID: 15980067
Christensen04: Christensen SK, Maenhaut-Michel G, Mine N, Gottesman S, Gerdes K, Van Melderen L (2004). "Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: involvement of the yefM-yoeB toxin-antitoxin system." Mol Microbiol 51(6);1705-17. PMID: 15009896
ChristensenDals08: Christensen-Dalsgaard M, Gerdes K (2008). "Translation affects YoeB and MazF messenger RNA interferase activities by different mechanisms." Nucleic Acids Res 36(20);6472-81. PMID: 18854355
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Feng13: Feng S, Chen Y, Kamada K, Wang H, Tang K, Wang M, Gao YG (2013). "YoeB-ribosome structure: a canonical RNase that requires the ribosome for its specific activity." Nucleic Acids Res 41(20);9549-56. PMID: 23945936
Grady03: Grady R, Hayes F (2003). "Axe-Txe, a broad-spectrum proteic toxin-antitoxin system specified by a multidrug-resistant, clinical isolate of Enterococcus faecium." Mol Microbiol 47(5);1419-32. PMID: 12603745
Kawano09: Kawano H, Hirokawa Y, Mori H (2009). "Long-term survival of Escherichia coli lacking the HipBA toxin-antitoxin system during prolonged cultivation." Biosci Biotechnol Biochem 73(1);117-23. PMID: 19129642
Kedzierska07: Kedzierska B, Lian LY, Hayes F (2007). "Toxin-antitoxin regulation: bimodal interaction of YefM-YoeB with paired DNA palindromes exerts transcriptional autorepression." Nucleic Acids Res 35(1);325-39. PMID: 17170003
Kim09a: Kim Y, Wang X, Ma Q, Zhang XS, Wood TK (2009). "Toxin-antitoxin systems in Escherichia coli influence biofilm formation through YjgK (TabA) and fimbriae." J Bacteriol 191(4);1258-67. PMID: 19060153
KolodkinGal09: Kolodkin-Gal I, Verdiger R, Shlosberg-Fedida A, Engelberg-Kulka H (2009). "A differential effect of E. coli toxin-antitoxin systems on cell death in liquid media and biofilm formation." PLoS One 4(8);e6785. PMID: 19707553
Leplae11: Leplae R, Geeraerts D, Hallez R, Guglielmini J, Dreze P, Van Melderen L (2011). "Diversity of bacterial type II toxin-antitoxin systems: a comprehensive search and functional analysis of novel families." Nucleic Acids Res 39(13);5513-25. PMID: 21422074
Polom13: Polom D, Boss L, Węgrzyn G, Hayes F, Kędzierska B (2013). "Amino acid residues crucial for specificity of toxin-antitoxin interactions in the homologous Axe-Txe and YefM-YoeB complexes." FEBS J 280(22);5906-18. PMID: 24028219
Pomerantsev01: Pomerantsev AP, Golovliov IR, Ohara Y, Mokrievich AN, Obuchi M, Norqvist A, Kuoppa K, Pavlov VM (2001). "Genetic organization of the Francisella plasmid pFNL10." Plasmid 46(3);210-22. PMID: 11735370
Tsilibaris07: Tsilibaris V, Maenhaut-Michel G, Mine N, Van Melderen L (2007). "What is the benefit to Escherichia coli of having multiple toxin-antitoxin systems in its genome?." J Bacteriol 189(17);6101-8. PMID: 17513477
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