An unsuspected autoregulatory pathway involving apocytochrome TorC and sensor TorS in Escherichia coli

Trimethylamine N-oxide (TMAO) respiration is carried out mainly by the Tor system in Escherichia coli. This system is encoded by the torCAD operon and comprises a periplasmic TMAO reductase (TorA) and a c-type cytochrome (Tor C), which shuttles electrons to TorA. Expression of the for operon is posit ively controlled by the TorS/TorR phosphorelay system in response to TMAO a vailability and negatively regulated by apocytochrome TorC. Interaction stu dies showed that, when immature, TorC can no longer bind TorA efficiently b ut can bind the periplasmic detector region of sensor TorS. ApoTorC negativ e autoregulation and TMAO induction are thus mediated by the same sensor pr otein. As apocyto-chromes related to TorC could not down-regulate the for o peron, we concluded that this negative control is highly specific. Moreover , the N-terminal half of apoTorC played no role in this control but the imm ature C-terminal domain of TorC strongly downregulated the for operon and i nteracted with the TorS detector region. This sophisticated autoregulatory pathway thus involves the C-terminal domain of apoTorC and allows optimal T orC biogenesis by preventing from saturation the c-type cytochrome maturati on machinery.