title: Periplasmic interaction between two membrane regulatory proteins, ToxR and ToxS, results in signal transduction and transcriptional activation.
abstract: ToxR is a transmembrane, DNA-binding protein that can activate transcription of genes encoding cholera toxin (ctxAB). Here we characterize ToxS, a 19 kd transmembrane regulatory protein that interacts with ToxR and stimulates its activity. If a portion of the periplasmic domain of ToxR is deleted, productive interaction with ToxS is abolished. A ToxR-PhoA fusion protein that retains most of the ToxR periplasmic region remains dependent on ToxS for its ToxR activity. ToxS protects this fusion from proteolytic cleavage, suggesting that these two proteins interact within the periplasm. Mutations in a short cytoplasmic domain of ToxR were isolated that disrupt the periplasmic interaction between ToxR and ToxS. This domain is shared by other bacterial transcriptional activators, suggesting that it may play a common role in function of these proteins and in the molecular mechanism of signal transduction.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: V J
authors.initials: VJ
authors.lastname: DiRita
authors.forename: J J
authors.initials: JJ
authors.lastname: Mekalanos
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D015153:Blotting, Western; D002772:Cholera Toxin / Q000235:genetics*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009876:Operon; D010957:Plasmids; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015183:Restriction Mapping; D015398:Signal Transduction; D014157:Transcription Factors; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C499324:toxR protein, Vibrio cholerae; C066719:toxR protein, bacteria; C066828:ToxS protein, Vibrio cholerae; D002772:Cholera Toxin; D000469:Alkaline Phosphatase; D001616:beta-Galactosidase