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Type II Toxin-Antitoxin Loci: The phd/doc Family

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Prokaryotic Toxin-Antitoxins

Abstract

The phd/doc family is one the smallest families of toxin–antitoxin modules and was first discovered as a plasmid addiction module on E. coli bacteriophage P1. The toxin Doc interacts with the ribosome, competes with hygromycin, and inhibits translation. Structurally, Doc resembles Fic domains, which are known to transfer an AMP moiety to the hydroxyphenyl group of a tyrosine in the target protein. Although much of the AMP/ATP binding site of Fic is conserved in Doc, no specific enzymatic activity has yet been linked to Doc. Nevertheless, mutations in the loop corresponding to the active site loop of Fic render Doc inactive. Regulation of the P1 phd/doc operon is understood in terms of a detailed molecular mechanism and involves conditional cooperativity. The N-terminal domain of Phd forms the DNA-binding unit and represents a common DNA-binding fold that is also shared with a number of antitoxins from different TA families, among which YefM is the best studied. Enhancement of the DNA-binding affinity of Phd by Doc stems both from allosteric coupling between the Doc- and DNA-binding sites on Phd and from avidity effects due to Doc-mediated bridging of two Phd dimers bound to the operator site. Activation of the system at high Doc-to-Phd ratios stems from a low-to-high affinity switch in the interaction between Phd and Doc.

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Authors and Affiliations

  1. Department of Structural Biology,VIB and Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, B-1050, Brussels, Belgium

    Abel Garcia-Pino, Yann Sterckx & Remy Loris

  2. Department of Biological Sciences, University of Alabama in Huntsville, 301 Sparkman Drive, SC 369R, Huntsville, AL 35758, USA

    Roy D. Magnuson

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  1. Abel Garcia-Pino
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  2. Yann Sterckx
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  3. Roy D. Magnuson
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  4. Remy Loris
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Correspondence to Remy Loris .

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  1. Inst. for Cell and Molecular Bioscience, Centre for Bacterial Cell Biology, Newcastle University, Richardson Road, Newcastle upon Tyne, NE2 4AX, United Kingdom

    Kenn Gerdes

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Garcia-Pino, A., Sterckx, Y., Magnuson, R.D., Loris, R. (2013). Type II Toxin-Antitoxin Loci: The phd/doc Family. In: Gerdes, K. (eds) Prokaryotic Toxin-Antitoxins. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-33253-1_9

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