The bacterial antitoxin HipB establishes a ternary complex with operator DNA and phosphorylated toxin HipA to regulate bacterial persistence.
Nucleic Acids Research. 2014-07-23; 42(15): 10134-10147
DOI: 10.1093/nar/gku665
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1. Nucleic Acids Res. 2014 Sep;42(15):10134-47. doi: 10.1093/nar/gku665. Epub 2014
Jul 23.
The bacterial antitoxin HipB establishes a ternary complex with operator DNA and
phosphorylated toxin HipA to regulate bacterial persistence.
Wen Y(1), Behiels E(2), Felix J(3), Elegheert J(3), Vergauwen B(3), Devreese
B(4), Savvides SN(5).
Author information:
(1)Unit for Biological Mass Spectrometry and Proteomics, Laboratory for Protein
Biochemistry and Biomolecular Engineering (L-ProBE), Ghent University, K.L.
Ledeganckstraat 35, 9000 Ghent, Belgium Unit for Structural Biology, Laboratory
for Protein Biochemistry and Biomolecular Engineering (L-ProBE), Ghent
University, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium.
(2)Unit for Biological Mass Spectrometry and Proteomics, Laboratory for Protein
Biochemistry and Biomolecular Engineering (L-ProBE), Ghent University, K.L.
Ledeganckstraat 35, 9000 Ghent, Belgium.
(3)Unit for Structural Biology, Laboratory for Protein Biochemistry and
Biomolecular Engineering (L-ProBE), Ghent University, K.L. Ledeganckstraat 35,
9000 Ghent, Belgium.
(4)Unit for Biological Mass Spectrometry and Proteomics, Laboratory for Protein
Biochemistry and Biomolecular Engineering (L-ProBE), Ghent University, K.L.
Ledeganckstraat 35, 9000 Ghent, Belgium .
(5)Unit for Structural Biology, Laboratory for Protein Biochemistry and
Biomolecular Engineering (L-ProBE), Ghent University, K.L. Ledeganckstraat 35,
9000 Ghent, Belgium .
Nearly all bacteria exhibit a type of phenotypic growth described as persistence
that is thought to underlie antibiotic tolerance and recalcitrant chronic
infections. The chromosomally encoded high-persistence (Hip) toxin-antitoxin
proteins HipASO and HipBSO from Shewanella oneidensis, a proteobacterium with
unusual respiratory capacities, constitute a type II toxin-antitoxin protein
module. Here we show that phosphorylated HipASO can engage in an unexpected
ternary complex with HipBSO and double-stranded operator DNA that is distinct
from the prototypical counterpart complex from Escherichia coli. The structure of
HipBSO in complex with operator DNA reveals a flexible C-terminus that is
sequestered by HipASO in the ternary complex, indicative of its role in binding
HipASO to abolish its function in persistence. The structure of HipASO in complex
with a non-hydrolyzable ATP analogue shows that HipASO autophosphorylation is
coupled to an unusual conformational change of its phosphorylation loop. However,
HipASO is unable to phosphorylate the translation factor Elongation factor Tu,
contrary to previous reports, but in agreement with more recent findings. Our
studies suggest that the phosphorylation state of HipA is an important factor in
persistence and that the structural and mechanistic diversity of HipAB modules as
regulatory factors in bacterial persistence is broader than previously thought.
© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic
Acids Research.
DOI: 10.1093/nar/gku665
PMCID: PMC4150777
PMID: 25056321 [Indexed for MEDLINE]