Heterodimeric structure of superoxide dismutase in complex with its metallochaperone

Area of Science:

• Biochemistry
• Structural Biology
• Enzymology

Background:

• Copper, zinc superoxide dismutase (SOD1) is a critical eukaryotic antioxidant enzyme.
• The copper chaperone for superoxide dismutase (CCS) is essential for SOD1 activation.

Purpose of the Study:

• To elucidate the structural basis of the interaction between yeast SOD1 and its chaperone, yeast CCS (yCCS).
• To understand the mechanism of copper ion transfer mediated by CCS to SOD1.

Main Methods:

• X-ray crystallography to determine the 2.9 A resolution structure of the yeast SOD1-yCCS complex.
• Analysis of protein-protein interfaces and conformational changes.

Main Results:

• The structure reveals a heterodimer of SOD1 and yCCS.
• The interface between SOD1 and yCCS is similar to homodimer interfaces.
• Significant conformational changes occur in both SOD1 and yCCS upon complex formation.
• The C-terminal domain of yCCS is positioned to facilitate copper transfer.
• An intermolecular disulfide bond links yCCS to SOD1, potentially regulating copper delivery.

Conclusions:

• The CCS-SOD1 complex structure provides insights into the mechanism of SOD1 activation.
• Conformational rearrangements and the C-terminal domain of CCS are crucial for copper delivery.
• The intermolecular disulfide bond may play a regulatory role in copper transfer.