Fig. 5.

Schematic mechanism of CCS-dependent hSOD1 maturation in vitro. (1) Nascent hSOD1 (E,E-hSOD^SH) acquires zinc from an unknown source, producing E,Zn-hSOD1^SH. (2) The hSOD1^SH monomer forms a heterodimer with a monomer Cu(I)-hCCS. The current study suggests that copper transfer (3) occurs before formation of the intermolecular (4), and then hSOD1 intramolecular (5), disulfide bond, resulting in the mature monomer (6) that dimerizes to the active state. Although oxygen in vitro is required in the process before step 4, it is currently unknown precisely at which step this occurs. [Note: E,Zn-hSOD1^SH can obtain Cu(I) in a CCS-independent manner.]