Crystal structure of the cyanobacterial metallothionein repressor SmtB: a model for metalloregulatory proteins

Abstract

SmtB from Synechococcus PCC7942 is a trans-acting dimeric repressor that is required for Zn2+-responsive expression of the metallothionein SmtA. The structure of SmtB was solved using multiple isomorphous replacement techniques and refined at 2.2 Å resolution by simulated annealing to an R-factor of 0.218. SmtB displays the classical helix-turn-helix motif found in many DNA-binding proteins. It has a α + β topology, and the arrangement of the three core helices and the beta hairpin is similar to the HNF-3/fork head, CAP and diphtheria toxin repressor proteins. Although there is no zinc in the crystal structure, analysis of a mercuric acetate derivative suggests a total of four Zn2+ binding sites in the dimer. Two of these putative sites are at the opposite ends of the dimer, while the other two are at the dimer interface and are formed by residues contributed from each monomer. The structure of the dimer is such that simultaneous binding for both recognition helices to DNA would require either a bend in the DNA helix or a conformational change in the dimer. The structure of Synechococcus SmtB is the first in this family of metal-binding DNA repressors.