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

Abel Garcia Pino, Yann Sterckx, Roy Magnuson, Remy Loris

Research output: Chapter in Book/Report/Conference proceedingChapter


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 involves conditional co-operativity and is understood in terms of a detailed molecular mechanism. 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 an avidity affect 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.
Original languageEnglish
Title of host publicationBiology of Prokaryotic Toxin-Antitoxins
EditorsK. Gerdes
PublisherSpringer Verlag
Number of pages20
ISBN (Print)978-3-642-33252-4
Publication statusPublished - 2012

Bibliographical note

K. Gerdes


  • Toxin-antitoxin module
  • Phd/Doc
  • Structural Biology
  • Intrinsic disorder


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