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The Haemophilus influenzae HipBA toxin-antitoxin system adopts an unusual three-com-ponent regulatory mechanism
Ji Sung Koo1, Sung-Min Kang2, Won-Min Jung1
1Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
Abstract:
Type II toxin-antitoxin (TA) systems encode two proteins: a toxin that inhibits cell growth and an antitoxin that neutralizes the toxin by direct inter-molecular protein-protein inter-actions. The bacterial HipBA TA system is implicated in persister formation. The Haemophilus influenzae HipBA TA system consists of a HipB antitoxin and a HipA toxin, the latter of which is split into two fragments, and here we investigate this novel three-com-ponent regulatory HipBA system. Structural and functional analysis revealed that HipAN corresponds to the N-ter-minal part of HipA from other bacteria and toxic HipAC is inactivated by HipAN, not HipB. This study will be helpful in understanding the detailed regulatory mechanism of the HipBAN+C system, as well as why it is constructed as a three-com-ponent system.
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