Year: 2013
Type: article
Abstract: Bacterial toxin-antitoxin (TA) systems regulate key cellular processes to promote cell survival during periods of stress. During steady-state cell growth, antitoxins typically interact with their cognate toxins to inhibit activity presumably by preventing substrate recognition. We solved two x-ray crystal structures of the Proteus vulgaris tetrameric HigB-(HigA)2-HigB TA complex and found that, unlike most other TA systems, the antitoxin HigA makes minimal interactions with toxin HigB. HigB adopts a RelE family tertiary fold containing a highly conserved concave surface where we predict its active site is located. HigA does not cover the solvent-exposed HigB active site, suggesting that, in general, toxin inhibition is not solely mediated by active site hindrance by its antitoxin. Each HigA monomer contains a helix-turn-helix motif that binds to its own DNA operator to repress transcription during normal cellular growth. This is distinct from antitoxins belonging to other superfamilies that typically only form DNA-binding motifs upon dimerization. We further show that disruption of the HigB-(HigA)2-HigB tetramer to a HigBA heterodimer ablates operator binding. Taken together, our biochemical and structural studies elucidate the novel molecular details of the HigBA TA system.
Source: Journal of Biological Chemistry
Institution: Emory University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: G102163711, G107546177, G1313983767, G1664757510, G2287611682, G262962599, G2784524989, Mechanism of HigB-mediated ribosome-dependent mRNA degradation, G3075337988, G3354192016, G3834503677, G498139845, G513797252, G5607048534, An Undulator Resource for Structural Biology, G6671297155, G6848031779, G6918803902, G7431513933, CAREER: Structure-function studies of bacterial toxin-ribosome complexes, TRAINING PROGRAM IN BIOCHEMISTRY, CELL AND DEVELOPMENT BIOLOGY, G9000221485, G969889393, G993149817
OpenAlex ID: W1963544294