Doc of prophage P1 is inhibited by its antitoxin partner Phd through fold complementation.

TitleDoc of prophage P1 is inhibited by its antitoxin partner Phd through fold complementation.
Publication TypeJournal Article
Year of Publication2008
AuthorsGarcia-Pino, A., M. Christensen-Dalsgaard, L. Wyns, M. Yarmolinsky, R. David Magnuson, K. Gerdes, and R. Loris
JournalJ Biol Chem
Date Published2008 Nov 7
Type of Articleta
KeywordsBacterial Toxins, Bacteriophage P1, Escherichia coli, Escherichia coli Proteins, Prophages, Protein Folding, Protein Structure, Quaternary, Protein Structure, Secondary, Protein Structure, Tertiary, RNA Interference, Viral Proteins

Prokaryotic toxin-antitoxin modules are involved in major physiological events set in motion under stress conditions. The toxin Doc (death on curing) from the phd/doc module on phage P1 hosts the C-terminal domain of its antitoxin partner Phd (prevents host death) through fold complementation. This Phd domain is intrinsically disordered in solution and folds into an alpha-helix upon binding to Doc. The details of the interactions reveal the molecular basis for the inhibitory action of the antitoxin. The complex resembles the Fic (filamentation induced by cAMP) proteins and suggests a possible evolutionary origin for the phd/doc operon. Doc induces growth arrest of Escherichia coli cells in a reversible manner, by targeting the protein synthesis machinery. Moreover, Doc activates the endogenous E. coli RelE mRNA interferase but does not require this or any other known chromosomal toxin-antitoxin locus for its action in vivo.

Alternate JournalJ. Biol. Chem.
Refereed DesignationRefereed
PubMed ID18757857
PubMed Central IDPMC2576525
Grant List2 R15 GM67668-03 / GM / NIGMS NIH HHS / United States
R15 GM067668 / GM / NIGMS NIH HHS / United States