Protein-protein communication: structural model of the repression complex formed by CytR and the global regulator CRP

The cAMP receptor protein (CRP) and the LacI-related CytR antiactivator bind cooperatively to adjacent DNA sites at or near promoters, an interaction that involves direct protein contacts. Here, we identify a collection of amino acid substitutions in CytR that reestablish protein-protein communication to mutant CRP proteins specifically defective in cooperative binding with wild-type CytR. To assess the location and spatial arrangement of these substitutions, we built a three-dimensional model of CytR based on the recent X-ray structure of the highly homologous PurR repressor bound to DNA. This approach enables us to specify the patch on CytR's surface that contacts CRP. Furthermore, our results permit the construction of a three-dimensional structure of the higher order nucleoprotein complex formed by CytR and CRP.