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==Crystal structure of the HigB1 toxin mutant K95A from Mycobacterium tuberculosis (Rv1955)==
==Crystal structure of the HigB1 toxin mutant K95A from Mycobacterium tuberculosis (Rv1955)==
<StructureSection load='7awk' size='340' side='right'caption='[[7awk]]' scene=''>
<StructureSection load='7awk' size='340' side='right'caption='[[7awk]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AWK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWK FirstGlance]. <br>
<table><tr><td colspan='2'>[[7awk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AWK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWK FirstGlance]. <br>
</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=7awk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awk OCA], [https://pdbe.org/7awk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awk RCSB], [https://www.ebi.ac.uk/pdbsum/7awk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awk ProSAT]</span></td></tr>
</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=7awk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awk OCA], [https://pdbe.org/7awk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awk RCSB], [https://www.ebi.ac.uk/pdbsum/7awk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awk ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/HIGB1_MYCTU HIGB1_MYCTU]] Toxic component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Upon expression in M.smegmatis inhibits colony formation and cell growth (PubMed:20011113, PubMed:23927792). Ectopic expression in wild-type M.tuberculosis has no effect on cell growth; ectopic expression in a triple higB1-higA1-Rv1957 (delta TAC) disruption mutant causes growth arrest, killing a considerable proportion of the cells. Increased ectopic expression leads to decreased levels of IdeR- and Zur-regulated genes as well as cleavage within the mRNA region of tmRNA (transfer-mRNA), strongly suggesting it is an endoribonuclease; also degrades E.coli and M-smegmatis tmRNA (PubMed:23927792). Its toxic effect is neutralized by coexpression with antitoxin HigA. Neutralization of HigB1 toxin in E.coli or M.marinum also requires SecB-like chaperone Rv1957, making this the first toxin-antitoxin chaperone (TAC) system (PubMed:21536872).<ref>PMID:19016878</ref> <ref>PMID:20011113</ref> <ref>PMID:21536872</ref> <ref>PMID:23927792</ref> 
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Bigot DJ]]
[[Category: Bigot, D J]]
[[Category: Guillet V]]
[[Category: Guillet, V]]
[[Category: Mourey L]]
[[Category: Mourey, L]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Rnase]]
[[Category: Toxin]]
[[Category: Toxin-antitoxin-chaperone]]

Revision as of 13:20, 18 May 2022

Crystal structure of the HigB1 toxin mutant K95A from Mycobacterium tuberculosis (Rv1955)Crystal structure of the HigB1 toxin mutant K95A from Mycobacterium tuberculosis (Rv1955)

Structural highlights

7awk is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HIGB1_MYCTU] Toxic component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Upon expression in M.smegmatis inhibits colony formation and cell growth (PubMed:20011113, PubMed:23927792). Ectopic expression in wild-type M.tuberculosis has no effect on cell growth; ectopic expression in a triple higB1-higA1-Rv1957 (delta TAC) disruption mutant causes growth arrest, killing a considerable proportion of the cells. Increased ectopic expression leads to decreased levels of IdeR- and Zur-regulated genes as well as cleavage within the mRNA region of tmRNA (transfer-mRNA), strongly suggesting it is an endoribonuclease; also degrades E.coli and M-smegmatis tmRNA (PubMed:23927792). Its toxic effect is neutralized by coexpression with antitoxin HigA. Neutralization of HigB1 toxin in E.coli or M.marinum also requires SecB-like chaperone Rv1957, making this the first toxin-antitoxin chaperone (TAC) system (PubMed:21536872).[1] [2] [3] [4]

References

  1. ↑ Gupta A. Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol Lett. 2009 Jan;290(1):45-53. doi:, 10.1111/j.1574-6968.2008.01400.x. Epub 2008 Nov 10. PMID:19016878 doi:http://dx.doi.org/10.1111/j.1574-6968.2008.01400.x
  2. ↑ 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
  3. ↑ Bordes P, Cirinesi AM, Ummels R, Sala A, Sakr S, Bitter W, Genevaux P. SecB-like chaperone controls a toxin-antitoxin stress-responsive system in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2011 May 17;108(20):8438-43. doi:, 10.1073/pnas.1101189108. Epub 2011 May 2. PMID:21536872 doi:http://dx.doi.org/10.1073/pnas.1101189108
  4. ↑ Schuessler DL, Cortes T, Fivian-Hughes AS, Lougheed KE, Harvey E, Buxton RS, Davis EO, Young DB. Induced ectopic expression of HigB toxin in Mycobacterium tuberculosis results in growth inhibition, reduced abundance of a subset of mRNAs and cleavage of tmRNA. Mol Microbiol. 2013 Oct;90(1):195-207. doi: 10.1111/mmi.12358. Epub 2013 Aug 23. PMID:23927792 doi:http://dx.doi.org/10.1111/mmi.12358

7awk, resolution 1.91Å

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