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

• Published in: The EMBO journal Vol. 18; no. 6; pp. 1435 - 1446
• Main Authors: Hall, David R., Gourley, David G., Leonard, Gordon A., Duke, Elizabeth M.H., Anderson, Lisa A., Boxer, David H., Hunter, William N.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 15.03.1999; Blackwell Publishing Ltd
• Subjects: Amino Acid Sequence; Bacterial Proteins; Binding Sites; Cloning, Molecular; Computer Graphics; Crystallography, X-Ray - methods; Dimerization; DNA - chemistry; DNA - metabolism; DNA binding; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins; gene regulation; Macromolecular Substances; Models, Molecular; Molecular Sequence Data; molybdate; Molybdenum - metabolism; Nucleic Acid Conformation; OB-fold; Protein Folding; Protein Structure, Secondary; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Selenomethionine; Software; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; winged helix-turn-helix
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/18.6.1435

The molybdate‐dependent transcriptional regulator (ModE) from Escherichia coli functions as a sensor of molybdate concentration and a regulator for transcription of operons involved in the uptake and utilization of the essential element, molybdenum. We have determined the structure of ModE using multi‐wavelength anomalous dispersion. Selenomethionyl and native ModE models are refined to 1.75 and 2.1 Å, respectively and describe the architecture and structural detail of a complete transcriptional regulator. ModE is a homodimer and each subunit comprises N‐ and C‐terminal domains. The N‐terminal domain carries a winged helix–turn–helix motif for binding to DNA and is primarily responsible for ModE dimerization. The C‐terminal domain contains the molybdate‐binding site and residues implicated in binding the oxyanion are identified. This domain is divided into sub‐domains a and b which have similar folds, although the organization of secondary structure elements varies. The sub‐domain fold is related to the oligomer binding‐fold and similar to that of the subunits of several toxins which are involved in extensive protein–protein interactions. This suggests a role for the C‐terminal domain in the formation of the ModE–protein–DNA complexes necessary to regulate transcription. Modelling of ModE interacting with DNA suggests that a large distortion of DNA is not necessary for complex formation.