The high-resolution crystal structure of the molybdate-dependent transcriptional regulator (ModE) from Escherichia coli: a novel combination of domain folds

The molybdate-dependent transcriptional regulator (ModE) from Escherichia c all functions as a sensor of molybdate concentration and a regulator for tr anscription of operons involved in the uptake and utilization of the essent ial element, molybdenum. We have determined the structure of ModE using mul ti-wavelength anomalous dispersion. Selenomethionyl and native ModE models are refined to 1.75 and 2.1 Angstrom, respectively and describe the archite cture and structural detail of a complete transcriptional regulator. ModE i s a homodimer and each subunit comprises N- and C-terminal domains. The N-t erminal domain carries a winged helix-turn-helix motif for binding to DNA a nd is primarily responsible for ModE dimerization. The C-terminal domain co ntains the molybdate-binding site and residues implicated in binding the ox yanion are identified. This domain is divided into sub-domains a and b whic h have similar folds, although the organization of secondary structure elem ents varies. The sub-domain fold is related to the oligomer binding-fold an d similar to that of the subunits of several toxins which are involved in e xtensive protein-protein interactions. This suggests a role for the C-termi nal domain in the formation of the ModE-protein-DNA complexes necessary to regulate transcription. Modelling of ModE interacting with DNA suggests tha t a large distortion of DNA is not necessary for complex formation.