4zlx
N-terminal DNA binding domain of the antitoxin Phd from phage P1
Structural highlights
FunctionPHD_BPP1 Antitoxin component of a toxin-antitoxin (TA) module. A labile antitoxin that binds to the doc toxin and neutralizes its toxic effect. Bacteriophage P1 lysogenizes bacteria as a low-copy number plasmid. Phd and doc proteins function in unison to stabilize plasmid number by inducing a lethal response to P1 plasmid prophage loss.[1] [2] Binds to its own promoter repressing its expression; toxin doc acts as a corepressor or derepressor depending on the ratio, repressing or inducing expression.[3] [4] Publication Abstract from PubMedConditional cooperativity is a common mechanism involved in transcriptional regulation of prokaryotic type II toxin-antitoxin operons and is intricately related to bacterial persistence. It allows the toxin component of a toxin-antitoxin module to act as a co-repressor at low doses of toxin as compared to antitoxin. When toxin level exceeds a certain threshold, however, the toxin becomes a de-repressor. Most antitoxins contain an intrinsically disordered region (IDR) that typically is involved in toxin neutralization and repressor complex formation. To address how the antitoxin IDR is involved in transcription regulation, we studied the phd-doc operon from bacteriophage P1. We provide evidence that the IDR of Phd provides an entropic barrier precluding full operon repression in the absence of Doc. Binding of Doc results in a cooperativity switch and consequent strong operon repression, enabling context-specific modulation of the regulatory process. Variations of this theme are likely to be a common mechanism in the autoregulation of bacterial operons that involve intrinsically disordered regions. An intrinsically disordered entropic switch determines allostery in Phd-Doc regulation.,Garcia-Pino A, De Gieter S, Talavera A, De Greve H, Efremov RG, Loris R Nat Chem Biol. 2016 May 2. doi: 10.1038/nchembio.2078. PMID:27159580[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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