Proposed Mbn signal transduction pathway featuring the MbnIRT triad. Mbn is secreted from the cell via the MATE multi-drug exporter MbnM and an unknown outer membrane partner. CuMbn is readmitted to the cell via the TonB-dependent transducer MbnT. CuMbn binding to MbnT induces a conformational change that results in contact with both the inner-membrane TonB-ExbD-ExbB complex and MbnR via the unique N-terminal extension of MbnT. CuMbn may or may not enter the cytoplasm intact, but either way, MbnR activates MbnI analogous to a standard FecIRA system. MbnI replaces σ70 in the active RNA polymerase complex, activating transcription of Mbn biosynthesis and transport genes, and potentially other operons needed in low copper conditions. In siderophore systems, the negative regulator Fur binds iron as intracellular iron levels rise, and the holo Fur binds to siderophore biosythesis and transport promoter regions, inhibiting transcription. A similar negative regulator might be needed to trigger the copper switch to pMMO production.
Kenney and Rosenzweig BMC Biology 2013 11:17 doi:10.1186/1741-7007-11-17