MEMBRANE INSERTION OF THE BACTERIAL SIGNAL-TRANSDUCTION PROTEIN TOXR AND REQUIREMENTS OF TRANSCRIPTION ACTIVATION STUDIED BY MODULAR REPLACEMENT OF DIFFERENT PROTEIN SUBSTRUCTURES

The Vibrio cholerae protein ToxR is an integral membrane protein that acts as a transcription activator in response to environmental signals; it controls expression of toxin genes ctxA and ctxB, along with a variety of other genes related to pathogenicity. Here it is shown that: (i) ToxR has a modular architecture and that activation of transcription starting at the ctx promoter depends strictly on dimerization of the periplasmic ToxR domain; (ii) the transmembrane (TM) region of ToxR is sufficient as a topogenic signal but not for stable membrane anchoring of the protein; (iii) the TM region has no special function in signal transduction and (iv) a proline residue located within the TM region minimizes background transcription activation, most plausibly by reducing TM-TM interaction. Possible applications of ToxR as a technical tool for analysing protein-protein interactions between pairs of arbitrary TM domains are discussed.