A copper-sensitive operon repressor protein (CsoR) has been identified in Streptomyces lividans (CsoRSl) and found to regulate copper homeostasis with attomolar affinity for Cu(I). Solution studies reveal apo- and CuI -CsoRSl to be a tetramer assembly, and a 1.7-A˚ resolution crystal structure of apo-CsoRSl reveals that a significant conformational change is necessary to enable Cu(I) binding.