Small Molecules Regulate Expression of Many Bacterial Genes via DNABinding Repressors

Transcription of most E. coli genes is regulated by processes similar to those described for the lac operon. The general mechanism involves a specific repressor that binds to the operator region of a gene or operon, thereby blocking transcription initiation. A small molecule (or molecules), called an inducer, binds to the repressor, controlling its DNA-binding activity and consequently the rate of transcription as appropriate for the needs of the cell.

For example, when the tryptophan concentration in the medium and cytosol is high, the cell does not synthesize the several enzymes encoded in the trp operon. Binding of tryp-tophan to the trp repressor causes a conformational change that allows the protein to bind to the trp operator, thereby repressing expression of the enzymes that synthesize trypto-phan. Conversely, when the tryptophan concentration in the medium and cytosol is low, tryptophan dissociates from the trp repressor, causing a conformational change in the protein that causes it to dissociate from the trp operator, allowing transcription of the trp operon. In the case of the lac operon, binding of the inducer lactose to the lac repressor reduces binding of the repressor to the operator, thereby promoting transcription.

Specific activator proteins, such as CAP in the lac operon, also control transcription of some but not all bacterial genes. These activators bind to DNA together with the RNA polymerase, stimulating transcription from a specific promoter. The DNA-binding activity of an activator is modulated in response to cellular needs by the binding of specific small molecules (e.g., cAMP) that alter the conformation of the activator.

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