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

• DOI: 10.1073/pnas.2500366122
• Publication Date: 2025-04-17T15:47:36Z
• Authors: Tatsuhiko Yokoyama; Ryoji Miyazaki; Takehiro Suzuki; Naoshi Dohmae; Hiroki Nagai; Tomoya Tsukazaki; Tomoko Kubori; Yoshinori Akiyama
• Keywords: Cleavage (geology)

TonB-dependent signal transduction is a versatile mechanism observed in gram-negative bacteria that integrates energy-dependent substrate transport with relay. In Escherichia coli , the TonB–ExbBD motor complex energizes outer membrane transporter FecA, facilitating ferric citrate import. FecA also acts as sensor, transmitting signals to cytoplasmic protein FecR, which eventually activates sigma factor FecI, driving transcription of fec operon. Building on our previous finding FecR undergoes functional maturation through three-step cleavage process [T. Yokoyama et al., J. Biol. Chem. 296 100673 (2021)], we here describe complete FecR-mediated signaling involving and TonB. The cascade begins autoproteolysis prior integration. soluble C-terminal domain (CTD) fragment cotranslocated N-terminal (NTD) twin-arginine translocation (Tat) system–mediated process. periplasm, interaction between CTD NTD fragments prevents further cleavage. Binding induces conformational change exposing its TonB box periplasmic space. This structural alteration transmitted interacting via function TonB, resulting release blockage from NTD. Consequently, successive FecR’s initiated, culminating signal–induced activation gene expression. Our findings reveal regulation cleavage, controlled by TonB–FecA axis, plays central role bacterial response signals.