Figure 4.

Proposed model for the molecular chaperone activity of CCS-D2. Schematic drawing of the initial maturation steps of SOD1 illustrating the role of CCS-D2 in stabilizing immature SOD1. The arrows show the preferred direction of each step. Red arrows indicate which maturation steps are negatively influenced by fALS-SOD1 mutations. Two possible mechanisms of action for CCS-D2 are shown: (a) SOD1 first binds zinc and then interacts with CCS-D2; (b) apo-SOD1 first interacts with CCS-D2 and then binds zinc. While the complex formed between SOD1 and CCS-D2 is stable and can be observed in the cells, the interaction between SOD1 and copper-bound FL-CCS (not shown) leads to the fully mature Cu,Zn-SOD1^SS protein.