Doc toxin is a kinase that inactivates elongation factor Tu
Jonathan W Cruz1, Francesca P Rothenbacher, Tatsuya Maehigashi
1From the Department of Biochemistry and Molecular Biology, Rutgers University, Robert Wood Johnson Medical School, and Rutgers Cancer Institute of New Jersey, Piscataway, New Jersey 08854.
The Journal of Biological Chemistry
|January 23, 2014
Summary
The Doc toxin, a pathogen-associated protein, acts as a kinase, phosphorylating elongation factor (EF)-Tu. This discovery reveals a novel mechanism for Fic domain proteins to inactivate GTPases, impacting bacterial toxin research.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Doc toxin, part of the phd-doc toxin-antitoxin system, is found in pathogens.
- Unlike other toxin-antitoxin systems, P1 Doc stabilizes mRNA rather than cleaving it.
- The mechanism of translation arrest by P1 Doc was previously unknown.
Purpose of the Study:
- To elucidate the molecular mechanism of P1 Doc toxin action.
- To investigate the role of the Fic domain in P1 Doc's function.
- To determine the target and modification type of P1 Doc.
Main Methods:
- Analysis of the P1 Doc toxin's Fic domain.
- Biochemical assays to identify the target of P1 Doc.
- Site-directed mutagenesis to pinpoint the phosphorylation site on EF-Tu.
Main Results:
- P1 Doc was identified as a kinase that phosphorylates elongation factor (EF)-Tu.
- Phosphorylation occurs at a conserved threonine residue (Thr-382) on EF-Tu.
- This phosphorylation site is inaccessible when EF-Tu is bound to kirromycin.
Conclusions:
- Fic domain proteins can function as kinases.
- P1 Doc inactivates EF-Tu via phosphorylation, a novel post-translational modification.
- All characterized Fic domain proteins target essential GTPases for inactivation.
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