ESCHERICHIA-COLI FTSH IS A MEMBRANE-BOUND, ATP-DEPENDENT PROTEASE WHICH DEGRADES THE HEAT-SHOCK TRANSCRIPTION FACTOR SIGMA(32)

Escherichia coil FtsH is an essential integral membrane protein that h as an AAA-type ATPase domain at its C-terminal cytoplasmic part, which is homologous to at least three ATPase subunits of the eukaryotic 26S proteasome. We report here that FtsH is involved in degradation of th e heat-shock transcription factor sigma(32), a key element in the regu lation of the E.coli heat-shock response. In the temperature-sensitive ftsH1 mutant, the amount of sigma(32) at a non-permissive temperature was higher than in the wild-type under certain conditions due to a re duced rate of degradation. In an in vitro system with purified compone nts, FtsH catalyzed ATP-dependent degradation of biologically active h istidine-tagged sigma(32). FtsH has a zinc-binding motif similar to th e active site of zinc-metalloproteases. Protease activity of FtsH for histidine-tagged sigma(32) was Stimulated by Zn2+ and strongly inhibit ed by the heavy metal chelating agent o-phenanthroline. We conclude th at FtsH is a novel membrane-bound, ATP-dependent metalloprotease with activity for sigma(32). These findings indicate a new mechanism of gen e regulation in E.coli.