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Publication Abstract from PubMed

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 find that, unlike most other TA systems, the antitoxin HigA makes minimal interactions with the 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 antitoxin binding. Each HigA monomer contains a helix-turn-helix (HTH) motif that binds to its own DNA operator to repress transcription during normal cellular growth. This is distinct from antitoxins belonging to other super families 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.

Structure of the P. vulgaris HigB-(HigA)2-HigB toxin-antitoxin complex.,Schureck MA, Maehigashi T, Miles SJ, Marquez J, Ei Cho S, Erdman R, Dunham CM J Biol Chem. 2013 Nov 20. PMID:24257752^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.