Heterodimeric structure of superoxide dismutase in complex with its metallochaperone

The copper chaperone for superoxide dismutase (CCS) activates the eukaryoti c antioxidant enzyme copper, zinc superoxide dismutase (SOD1). The 2.9 Angs trom resolution structure of yeast SOD1 complexed with yeast CCS (yCCS) rev eals that SOD I interacts with its metallochaperone to form a complex compr ising one monomer of each protein. The heterodimer interface is remarkably similar to the SOD1 and yCCS homodimer interfaces. Striking conformational rearrangements are observed in both the chaperone and target enzyme upon co mplex formation, and the functionally essential C-terminal domain of yCCS i s well positioned to play a key role in the metal ion transfer mechanism. T his domain is linked to SOD I by an intermolecular disulfide bond that may facilitate or regulate copper delivery.