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YeeV is an Escherichia coli toxin that inhibits cell division by targeting the cytoskeleton proteins, FtsZ and MreB.
Mol Microbiol. 2011 Jan; 79(1):109-18
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01 Feb 2011
William Margolin
F1000 Microbiology
University of Texas at Houston, Medical School,
Houston, TX, USA.
F1000 Microbiology
University of Texas at Houston, Medical School,
Houston, TX, USA.
DOI: 10.3410/f.7958957.8323055
This article is interesting because it characterizes an Escherichia coli protein, YeeV, which is part of a toxin-antitoxin pair that inhibits both MreB and FtsZ.
MreB and FtsZ are bacterial homologs of actin and tubulin, respectively, and form cytoskeletal filaments. MreB filaments, which extend as a...Continue reading
MreB and FtsZ are bacterial homologs of actin and tubulin, respectively, and form cytoskeletal filaments. MreB filaments, which extend as a...Continue reading
This article is interesting because it characterizes an Escherichia coli protein, YeeV, which is part of a toxin-antitoxin pair that inhibits both MreB and FtsZ.
MreB and FtsZ are bacterial homologs of actin and tubulin, respectively, and form cytoskeletal filaments. MreB filaments, which extend as a coiled structure throughout the cell's length, are important for the maintenance of cellular rod shape via control of cell diameter. FtsZ filaments, on the other hand, form a septal ring that is required for cytokinesis. Although a null mutation in yeeV has no phenotype, a previous study showed that overproduction of YeeV stopped cell growth {1}.
Here, the authors show that this growth arrest results from inhibition of both MreB and FtsZ activity by YeeV. YeeV-producing cells become filamentous but, also, expand in spherical patches, consistent with inhibition of cell division and cell diameter control. YeeV interacts with both MreB and FtsZ by pull-down assays, co-immunoprecipitation, and yeast two-hybrid analysis. Moreover, YeeV inhibits assembly of FtsZ polymers and MreB polymers in sedimentation assays. Interestingly, there is some evidence that the N-terminal portion of YeeV interacts with FtsZ, but not MreB, and that the C-terminal portion of YeeV interacts with MreB, but not FtsZ, although this will need further work to pin down. It also was not shown how MreB or FtsZ cytoskeletal filaments are affected in E. coli cells, but the in vitro data suggest that the filaments are destabilized. The readability of this paper was its one drawback, though it is worthwhile persevering for the interest and relevance of the findings.
In conclusion, the discovery of an E. coli peptide that inhibits both major cytoskeletal filaments in E. coli is intriguing, and it is anticipated that it may be a useful tool for understanding the function of these two proteins. In particular, the toxin may affect the direct FtsZ-MreB interaction (there is some evidence for this is in this paper). This direct interaction may occur during redistribution of the MreB coil to rings near FtsZ at mid-cell during cell division. The physiological function of the YeeV toxin, and when it might be induced, remain obscure.
MreB and FtsZ are bacterial homologs of actin and tubulin, respectively, and form cytoskeletal filaments. MreB filaments, which extend as a coiled structure throughout the cell's length, are important for the maintenance of cellular rod shape via control of cell diameter. FtsZ filaments, on the other hand, form a septal ring that is required for cytokinesis. Although a null mutation in yeeV has no phenotype, a previous study showed that overproduction of YeeV stopped cell growth {1}.
Here, the authors show that this growth arrest results from inhibition of both MreB and FtsZ activity by YeeV. YeeV-producing cells become filamentous but, also, expand in spherical patches, consistent with inhibition of cell division and cell diameter control. YeeV interacts with both MreB and FtsZ by pull-down assays, co-immunoprecipitation, and yeast two-hybrid analysis. Moreover, YeeV inhibits assembly of FtsZ polymers and MreB polymers in sedimentation assays. Interestingly, there is some evidence that the N-terminal portion of YeeV interacts with FtsZ, but not MreB, and that the C-terminal portion of YeeV interacts with MreB, but not FtsZ, although this will need further work to pin down. It also was not shown how MreB or FtsZ cytoskeletal filaments are affected in E. coli cells, but the in vitro data suggest that the filaments are destabilized. The readability of this paper was its one drawback, though it is worthwhile persevering for the interest and relevance of the findings.
In conclusion, the discovery of an E. coli peptide that inhibits both major cytoskeletal filaments in E. coli is intriguing, and it is anticipated that it may be a useful tool for understanding the function of these two proteins. In particular, the toxin may affect the direct FtsZ-MreB interaction (there is some evidence for this is in this paper). This direct interaction may occur during redistribution of the MreB coil to rings near FtsZ at mid-cell during cell division. The physiological function of the YeeV toxin, and when it might be induced, remain obscure.
References
1.
A novel family of Escherichia coli toxin-antitoxin gene pairs.
J Bacteriol 2003 Nov; 22(185):6600-8
PMID: 14594833
Disclosures
None declared
Add Comment
Margolin W: F1000Prime Recommendation of [Tan Q et al., Mol Microbiol 2011, 79(1):109-18]. In F1000Prime, 01 Feb 2011; DOI: 10.3410/f.7958957.8323055. F1000Prime.com/7958957#eval8323055
18 Feb 2011
Novel Drug Target
DOI: 10.3410/f.7958957.8788056
In this interesting paper, the authors describe a novel toxin-antitoxin locus (TA locus). Surprisingly, unlike anything previously known, this newly discovered toxin (from the TA locus) affects two different cytoskeletal proteins, FtsZ (tubulin) and MreB (actin).
The toxin YeeV from the YeeUV-TA locus...Continue reading
The toxin YeeV from the YeeUV-TA locus...Continue reading
In this interesting paper, the authors describe a novel toxin-antitoxin locus (TA locus). Surprisingly, unlike anything previously known, this newly discovered toxin (from the TA locus) affects two different cytoskeletal proteins, FtsZ (tubulin) and MreB (actin).
The toxin YeeV from the YeeUV-TA locus in Escherichia coli physically associates with both FtsZ and MreB and blocks their polymerization. Curiously, however, YeeV blocked the GTPase activity of FtsZ, but not the ATPase activity of MreB, suggesting different modes of inhibition. While most FtsZ-interacting proteins bind the C-terminal tail of FtsZ, SulA (a potent cell cytokinesis inhibitor upon DNA damage) requires the N-terminal region for binding. Interestingly, the authors also find that YeeV requires both the N-terminal and C-terminal regions of FtsZ for binding. The authors further show that while the C-termini of YeeV might be the cause for cell-division block through FtsZ, the N-terminus could be responsible for binding to MreB. Although the physiological functions of TA systems in general are not yet fully understood, this surprising finding that a toxin of the TA system acts through the cytoskeleton is interesting. One might speculate as to how such TA systems, once in place, might potentially be incorporated into adaptation responses or developmental regulation.
The toxin YeeV from the YeeUV-TA locus in Escherichia coli physically associates with both FtsZ and MreB and blocks their polymerization. Curiously, however, YeeV blocked the GTPase activity of FtsZ, but not the ATPase activity of MreB, suggesting different modes of inhibition. While most FtsZ-interacting proteins bind the C-terminal tail of FtsZ, SulA (a potent cell cytokinesis inhibitor upon DNA damage) requires the N-terminal region for binding. Interestingly, the authors also find that YeeV requires both the N-terminal and C-terminal regions of FtsZ for binding. The authors further show that while the C-termini of YeeV might be the cause for cell-division block through FtsZ, the N-terminus could be responsible for binding to MreB. Although the physiological functions of TA systems in general are not yet fully understood, this surprising finding that a toxin of the TA system acts through the cytoskeleton is interesting. One might speculate as to how such TA systems, once in place, might potentially be incorporated into adaptation responses or developmental regulation.
Disclosures
None declared
Balasubramanian M, Srinivasan R and Mishra M: F1000Prime Recommendation of [Tan Q et al., Mol Microbiol 2011, 79(1):109-18]. In F1000Prime, 18 Feb 2011; DOI: 10.3410/f.7958957.8788056. F1000Prime.com/7958957#eval8788056
F1000Prime Recommendations, Dissents and Comments for [Tan Q et al., Mol Microbiol 2011, 79(1):109-18]. In F1000Prime, 19 May 2013; F1000Prime.com/7958957
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Toxin-antitoxin (TA) systems of free-living bacteria have recently demonstrated that these toxins inhibit cell growth by targeting essential functions of cellular metabolism. Here we show that YeeV toxin inhibits cell division, leads to a change in morphology and lysis of Escherichia coli cells. YeeV interacts with two essential cytoskeleton proteins, FtsZ and MreB. Purified YeeV inhibits both the GTPase activity and the GTP-dependent polymerization of FtsZ. YeeV also inhibits ATP-dependent polymerization of MreB. Truncated C-terminal deletions of YeeV result in elongation of cells, and a deletion of the first 15 amino acids from the N-terminus of YeeV caused lemon-shaped cell formation. The YeeV toxin is distinct from other well-studied toxins: it directs the binding of two cytoskeletal proteins and inhibits FtsZ and MreB simultaneously.
© 2010 Blackwell Publishing Ltd.
DOI: 10.1111/j.1365-2958.2010.07433.x
PMID: 21166897
