Crystal Structure of the Transcription Regulator RsrR Reveals a [2Fe-2S] Cluster Coordinated by Cys， Glu， and His Residues.

The recently discovered Rrf2 family transcriptional regulator RsrR coordinates a [2Fe-2S] cluster. Remarkably， binding of the protein to RsrR-regulated promoter DNA sequences is switched on and off through the facile cycling of the [2Fe-2S] cluster between +2 and +1 states. Here， we report high resolution crystal structures of the RsrR dimer， revealing that the [2Fe-2S] cluster is asymmetrically coordinated across the RsrR monomer-monomer interface by two Cys residues from one subunit and His and Glu residues from the other. To our knowledge， this is the first example of a protein bound [Fe-S] cluster with three different amino acid side chains as ligands， and of Glu acting as ligand to a [2Fe-2S] cluster. Analyses of RsrR structures revealed a conformational change， centered on Trp9， which results in a significant shift in the DNA-binding helix-turn-helix region.