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6hpb

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Crystal structure of the E.coli HicAB toxin-antitoxin complex

Structural highlights

6hpb is a 4 chain structure with sequence from Escherichia coli 2-222-05_S4_C3 and Escherichia coli str. K-12 substr. MG1655. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.28Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HICA_ECOLI Toxic component of a type II toxin-antitoxin (TA) system. A probable translation-independent mRNA interferase. Overexpression causes cessation of cell growth and inhibits cell proliferation via inhibition of translation; this blockage is overcome (after 90 minutes) by subsequent expression of antitoxin HicB. Overexpression causes cleavage of a number of mRNAs and tmRNA, in a translation-independent fashion, suggesting this is an mRNA interferase (PubMed:19060138). mRNA interferases play a role in bacterial persistence to antibiotics (PubMed:21788497).^[1] ^[2]

Publication Abstract from PubMed

The E. coli hicAB type II toxin-antitoxin locus is unusual by being controlled by two promoters and by having the toxin encoded upstream of the antitoxin. HicA toxins contain a double-stranded RNA-binding fold and cleaves both mRNA and tmRNA in vivo, while HicB antitoxins contain a partial RNase H fold and either a helix-turn-helix (HTH) or ribbon-helix-helix domain. It is not known how an HTH DNA-binding domain affects higher-order structure for the HicAB modules. Here, we present crystal structures of the isolated E. coli HicB antitoxin and full-length HicAB complex showing that HicB forms a stable DNA-binding module and interacts in a canonical way with HicA despite the presence of an HTH-type DNA-binding domain. No major structural rearrangements take place upon binding of the toxin. Both structures expose well-ordered DNA-binding motifs allowing a model for DNA binding by the antitoxin to be generated.

The E. coli HicB Antitoxin Contains a Structurally Stable Helix-Turn-Helix DNA Binding Domain.,Manav MC, Turnbull KJ, Jurenas D, Garcia-Pino A, Gerdes K, Brodersen DE Structure. 2019 Sep 4. pii: S0969-2126(19)30279-5. doi:, 10.1016/j.str.2019.08.008. PMID:31495532^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jorgensen MG, Pandey DP, Jaskolska M, Gerdes K. HicA of Escherichia coli defines a novel family of translation-independent mRNA interferases in bacteria and archaea. J Bacteriol. 2009 Feb;191(4):1191-9. doi: 10.1128/JB.01013-08. Epub 2008 Dec 5. PMID:19060138 doi:http://dx.doi.org/10.1128/JB.01013-08
↑ Maisonneuve E, Shakespeare LJ, Jorgensen MG, Gerdes K. Bacterial persistence by RNA endonucleases. Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13206-11. doi:, 10.1073/pnas.1100186108. Epub 2011 Jul 25. PMID:21788497 doi:http://dx.doi.org/10.1073/pnas.1100186108
↑ Manav MC, Turnbull KJ, Jurenas D, Garcia-Pino A, Gerdes K, Brodersen DE. The E. coli HicB Antitoxin Contains a Structurally Stable Helix-Turn-Helix DNA Binding Domain. Structure. 2019 Sep 4. pii: S0969-2126(19)30279-5. doi:, 10.1016/j.str.2019.08.008. PMID:31495532 doi:http://dx.doi.org/10.1016/j.str.2019.08.008