Structural basis of transcriptional regulation by the HigA antitoxin.
Journal
Molecular microbiology
ISSN: 1365-2958
Titre abrégé: Mol Microbiol
Pays: England
ID NLM: 8712028
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
accepted:
16
02
2019
pubmed:
23
2
2019
medline:
15
2
2020
entrez:
23
2
2019
Statut:
ppublish
Résumé
Bacterial toxin-antitoxin systems are important factors implicated in growth inhibition and plasmid maintenance. Type II toxin-antitoxin pairs are regulated at the transcriptional level by the antitoxin itself. Here, we examined how the HigA antitoxin regulates the expression of the Proteus vulgaris higBA toxin-antitoxin operon from the Rts1 plasmid. The HigBA complex adopts a unique architecture suggesting differences in its regulation as compared to classical type II toxin-antitoxin systems. We find that the C-terminus of the HigA antitoxin is required for dimerization and transcriptional repression. Further, the HigA structure reveals that the C terminus is ordered and does not transition between disorder-to-order states upon toxin binding. HigA residue Arg40 recognizes a TpG dinucleotide in higO2, an evolutionary conserved mode of recognition among prokaryotic and eukaryotic transcription factors. Comparison of the HigBA and HigA-higO2 structures reveals the distance between helix-turn-helix motifs of each HigA monomer increases by ~4 Å in order to bind to higO2. Consistent with these data, HigBA binding to each operator is twofold less tight than HigA alone. Together, these data show the HigB toxin does not act as a co-repressor suggesting potential novel regulation in this toxin-antitoxin system.
Identifiants
pubmed: 30793388
doi: 10.1111/mmi.14229
pmc: PMC6561789
mid: NIHMS1013303
doi:
Substances chimiques
Bacterial Proteins
0
HigA protein, Proteus vulgaris
0
HigB protein, Proteus vulgaris
0
Repressor Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1449-1462Subventions
Organisme : NIGMS NIH HHS
ID : F31 GM108351
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103403
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008367
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR029205
Pays : United States
Informations de copyright
© 2019 John Wiley & Sons Ltd.
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