Structural basis for DNA recognition and binding specificity by the transcription factor Ets2

Abstract

cotranscribed genes, termed the mercury resistance mer operon, allows them to survive in environments contain mercurial compounds. The mer operon encodes proteins capable of converting inorganic (Hg(II)) and organiomercurial compounds (such as methylmercury, MeHg) to less toxic form (Hg(0)). The mer operon transcription is activated by MerR family protein. MerR family protein turns into a transcription activator upon Hg(II) binding. To understand how MerR family protein regulates the transcription of mer operon, we have determined the structure of MerR family protein from Gram-positive bacteria Bacillus megaterium MB1 by the multiwavelength anomalous diffraction method. The MerR family protein monomer contains a DNA-binding domain, a dimerization helix and a metal-binding motif. Like most other transcription activators, dimerization of MerR family protein is required for function. A total of four MerR family protein dimers are present in the asymmetric unit, all exhibiting similar quaternary structure. The N-terminal DNA-binding domain contains three helices which form a helix-turn-helix motif. The motif is followed by an 8-residue loop and the dimerization domain that is composed of an 8.5-turn alfa-helix. Dimerization of MerR family protein is mediated by packing the two long helices as an antiparallel coiled-coil. The C-terminal metal-binding motif is quite small, consisted of two 3 10 helices and two connecting residues. A total of four MerR family protein dimers are present in the asymmetric unit, all exhibiting similar quaternary structure. Compared with the structures of other MerR family members, our structure suggests that Hg(II) binding may alter the quaternary structure of MerR family protein. Such a structural transition may reposition the two DNA-binding domains, thus allows the promoter DNA to interact productively with the RNA polymerase to turn on transcription.