Paper

Cleavage cascade of the sigma regulator FecR orchestrates TonB-dependent signal transduction

Suzuki, Takehiro, Tsukazaki, Tomoya, Nagai, Hiroki, Akiyama, Yoshinori, Dohmae, Naoshi, Yokoyama, Tatsuhiko, Kubori, Tomoko, Miyazaki, Ryoji

2025

Overview

TonB-dependent signal transduction is a versatile mechanism observed in gram-negative bacteria, integrating energy-dependent substrate transport with signal relay. In Escherichia coli, the TonB-ExbBD motor complex energizes the TonB-dependent transporter FecA, facilitating ferric citrate import. FecA also functions as a sensor, transmitting signals to the cytoplasmic membrane protein FecR. We previously demonstrated that FecR undergoes a three-step cleavage process, culminating in the activation of the cytoplasmic sigma factor FecI, which drives fec gene transcription. Here, we describe the complete mechanism of FecR cleavage-mediated ferric citrate signaling involving FecA and TonB. The cleavage cascade begins with FecR autoproteolysis prior to membrane integration. The soluble C-terminal domain (CTD) fragment of FecR is co-translocated with the N-terminal domain (NTD) fragment through a Tat system-mediated process. In the periplasm, the interaction between the CTD and NTD fragments prevents further cleavage. This inhibition is lifted by TonB-mediated motor function, which releases the CTD, allowing the cleavage cascade to proceed. This process is essential for ferric citrate signal-induced activation of fec gene expression. Our findings reveal that the regulation of FecR cleavage, relying on the TonB-FecA axis, plays a central role in bacterial response to ferric citrate signals.Competing Interest StatementThe authors have declared no competing interest.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Citric acid / Cytoplasmic membranes / Ferric citrate / Gene expression / Gram-negative bacteria / Immunology / Periplasm / Protein transport / Sigma factor / Signal transduction / Transcription activation