Molecular mechanisms for activating transcription by E. Coli RNA ploymerase

Mechanistic and structural studies of one of the first characterized metalloregulatory proteins, MerR have revealed an unusual allosteric mechanism for stress responsive regulation of the catalytic activity of RNA polymerase. MerR exerts both positive and negative control over transcription of bacterial mercury resistance operons. This small, 144-residue protein represses gene expression in the absence of mercury and apparently activates gene expression in the presence of mercury via a DNA distortion mechanism. Other members of the MerR family of transcriptional activators, including the SoxR protein may control stress responsive in a similar manner. In the MerR case, an allosteric change in protein conformation is induced by Hg(II) binding and then transmitted to the transcriptional machinery through a MerR-induced change in DNA conformation. Essentially, Hg-MerR changes both the twist and bend of its DNA binding site in order to convert the promoter a better substrate for the RNA polymerase. It is likely that other transcription factors, such as TBP can stimulate polymerase activity by altering the writhe and twist of the promoter to lower the energetic barrier for stand separation in the open complex.