Structural basis of transcriptional regulation by the HigA antitoxin
Abstract
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. In this work, 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.
- Authors:
-
- Emory Univ. School of Medicine, Atlanta,GA (United States)
- Children’s Healthcare of Atlanta, GA (United States); Emory Univ. School of Medicine, Atlanta, GA (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- National Science Foundation (NSF); National Institutes of Health (NIH); Burroughs Wellcome Fund; National Institute of General Medical Sciences (NIGMS); Office of Research Infrastructure Programs (ORIP)
- OSTI Identifier:
- 1529630
- Grant/Contract Number:
- MCB 0953714; 5T32GM8367; GM108351; P41 GM103403; S10 RR029205; AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Molecular Microbiology
- Additional Journal Information:
- Journal Volume: 111; Journal Issue: 6; Journal ID: ISSN 0950-382X
- Publisher:
- Wiley
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Schureck, Marc A., Meisner, Jeffrey, Hoffer, Eric D., Wang, Dongxue, Onuoha, Nina, Ei Cho, Shein, Lollar III, Pete, and Dunham, Christine M. Structural basis of transcriptional regulation by the HigA antitoxin. United States: N. p., 2019.
Web. doi:10.1111/mmi.14229.
Schureck, Marc A., Meisner, Jeffrey, Hoffer, Eric D., Wang, Dongxue, Onuoha, Nina, Ei Cho, Shein, Lollar III, Pete, & Dunham, Christine M. Structural basis of transcriptional regulation by the HigA antitoxin. United States. https://doi.org/10.1111/mmi.14229
Schureck, Marc A., Meisner, Jeffrey, Hoffer, Eric D., Wang, Dongxue, Onuoha, Nina, Ei Cho, Shein, Lollar III, Pete, and Dunham, Christine M. Thu .
"Structural basis of transcriptional regulation by the HigA antitoxin". United States. https://doi.org/10.1111/mmi.14229. https://www.osti.gov/servlets/purl/1529630.
@article{osti_1529630,
title = {Structural basis of transcriptional regulation by the HigA antitoxin},
author = {Schureck, Marc A. and Meisner, Jeffrey and Hoffer, Eric D. and Wang, Dongxue and Onuoha, Nina and Ei Cho, Shein and Lollar III, Pete and Dunham, Christine M.},
abstractNote = {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. In this work, 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.},
doi = {10.1111/mmi.14229},
journal = {Molecular Microbiology},
number = 6,
volume = 111,
place = {United States},
year = {Thu Feb 21 00:00:00 EST 2019},
month = {Thu Feb 21 00:00:00 EST 2019}
}
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