6CHV

Proteus vulgaris HigA antitoxin bound to DNA

Summary for 6CHV

• Entry DOI: 10.2210/pdb6chv/pdb
• Descriptor: Antitoxin HigA, pHigCryst3, pHigCryst4, ... (5 entities in total)
• Functional Keywords: helix-turn-helix dna binding protein, dna-protein complex, toxin-antitoxin systems, antitoxin, antitoxin-dna complex, antitoxin/dna
• Biological source: Proteus vulgaris; More
• Total number of polymer chains: 12
• Total formula weight: 118075.87

Authors

Schureck, M.A.,Hoffer, E.D.,Onuoha, N.,Dunham, C.M. (deposition date: 2018-02-23, release date: 2019-02-27, Last modification date: 2023-10-04)

Primary citation

Schureck, M.A.,Meisner, J.,Hoffer, E.D.,Wang, D.,Onuoha, N.,Ei Cho, S.,Lollar 3rd, P.,Dunham, C.M.
Structural basis of transcriptional regulation by the HigA antitoxin.
Mol.Microbiol., 111:1449-1462, 2019

PubMed 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. 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.

PubMed: 30793388
DOI: 10.1111/mmi.14229

Experimental method

X-RAY DIFFRACTION (2.9 Å)