| Structural highlights
Function
[Y3357_MYCTU] Antitoxin component of a toxin-antitoxin (TA) module. A probable antitoxin for the putative mRNA interferase RelK. Upon expression in E.coli but not in M.smegmatis this protein neutralizes E.coli YoeB.[1] [2] [3] [4] Binds to and represses its own promoter, in combination with RelK repression is somewhat lessened. Several DNA-protein complexes are formed in vitro depending on the RelJ:RelK ratio.[5] [6] [7] [8]
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
Toxin-antitoxin modules are present on chromosomes of almost all free-living prokaryotes. Some are implicated to act as stress-responsive elements, among their many functional roles. The YefM-YoeB toxin-antitoxin system is present in many bacterial species, where YefM belongs to the Phd family antidote of phage P1, whereas YoeB is a homolog of the RelE toxin of the RelBE system, rather than the Doc system of phage P1. YoeB, a ribonuclease, is believed to be conformationally stable, whereas YefM has been proposed to be a member of intrinsically disordered proteins. The ribonucleolytic activity of YoeB is neutralized by YefM upon formation of the YefM-YoeB complex. We report here the crystal structure of Mycobacterium tuberculosis YefM from two crystal isoforms. Our crystallographic and biophysical studies reveal that YefM is not an intrinsically unfolded protein and instead forms a well-defined structure with significant secondary and tertiary structure conformations. The residues involved in core formation of the folded structure are evolutionarily conserved among many bacterial species, supporting our observation. The C-terminal end of its polypeptide is highly pliable, which adopts different conformations in different monomers. Since at the physiological level YefM controls the activity of YoeB through intricate protein-protein interactions, the conformational heterogeneity in YefM revealed by our structure suggests that these might act a master switch in controlling YoeB activity.
Crystal structure of Mycobacterium tuberculosis YefM antitoxin reveals that it is not an intrinsically unstructured protein.,Kumar P, Issac B, Dodson EJ, Turkenburg JP, Mande SC J Mol Biol. 2008 Nov 14;383(3):482-93. Epub 2008 Sep 4. PMID:18793646[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Korch SB, Contreras H, Clark-Curtiss JE. Three Mycobacterium tuberculosis Rel toxin-antitoxin modules inhibit mycobacterial growth and are expressed in infected human macrophages. J Bacteriol. 2009 Mar;191(5):1618-30. doi: 10.1128/JB.01318-08. Epub 2008 Dec 29. PMID:19114484 doi:http://dx.doi.org/10.1128/JB.01318-08
- ↑ Ramage HR, Connolly LE, Cox JS. Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 2009 Dec;5(12):e1000767. doi: 10.1371/journal.pgen.1000767. Epub 2009, Dec 11. PMID:20011113 doi:http://dx.doi.org/10.1371/journal.pgen.1000767
- ↑ Yang M, Gao C, Wang Y, Zhang H, He ZG. Characterization of the interaction and cross-regulation of three Mycobacterium tuberculosis RelBE modules. PLoS One. 2010 May 17;5(5):e10672. doi: 10.1371/journal.pone.0010672. PMID:20498855 doi:http://dx.doi.org/10.1371/journal.pone.0010672
- ↑ Kumar P, Issac B, Dodson EJ, Turkenburg JP, Mande SC. Crystal structure of Mycobacterium tuberculosis YefM antitoxin reveals that it is not an intrinsically unstructured protein. J Mol Biol. 2008 Nov 14;383(3):482-93. Epub 2008 Sep 4. PMID:18793646 doi:http://dx.doi.org/S0022-2836(08)01085-1
- ↑ Korch SB, Contreras H, Clark-Curtiss JE. Three Mycobacterium tuberculosis Rel toxin-antitoxin modules inhibit mycobacterial growth and are expressed in infected human macrophages. J Bacteriol. 2009 Mar;191(5):1618-30. doi: 10.1128/JB.01318-08. Epub 2008 Dec 29. PMID:19114484 doi:http://dx.doi.org/10.1128/JB.01318-08
- ↑ Ramage HR, Connolly LE, Cox JS. Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 2009 Dec;5(12):e1000767. doi: 10.1371/journal.pgen.1000767. Epub 2009, Dec 11. PMID:20011113 doi:http://dx.doi.org/10.1371/journal.pgen.1000767
- ↑ Yang M, Gao C, Wang Y, Zhang H, He ZG. Characterization of the interaction and cross-regulation of three Mycobacterium tuberculosis RelBE modules. PLoS One. 2010 May 17;5(5):e10672. doi: 10.1371/journal.pone.0010672. PMID:20498855 doi:http://dx.doi.org/10.1371/journal.pone.0010672
- ↑ Kumar P, Issac B, Dodson EJ, Turkenburg JP, Mande SC. Crystal structure of Mycobacterium tuberculosis YefM antitoxin reveals that it is not an intrinsically unstructured protein. J Mol Biol. 2008 Nov 14;383(3):482-93. Epub 2008 Sep 4. PMID:18793646 doi:http://dx.doi.org/S0022-2836(08)01085-1
- ↑ Kumar P, Issac B, Dodson EJ, Turkenburg JP, Mande SC. Crystal structure of Mycobacterium tuberculosis YefM antitoxin reveals that it is not an intrinsically unstructured protein. J Mol Biol. 2008 Nov 14;383(3):482-93. Epub 2008 Sep 4. PMID:18793646 doi:http://dx.doi.org/S0022-2836(08)01085-1
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