Folding of human superoxide dismutase: disulfide reduction prevents dimerization and produces marginally stable monomers.

ABSTRACT: The molecular mechanism by which the homodimeric enzyme Cu/Zn superoxide dismutase (SOD) causes neural damage in amytrophic lateral sclerosis is yet poorly understood. A striking, as well as an unusual, feature of SOD is that it maintains intrasubunit disulfide bonds in the reducing environment of the cytosol. Here, we investigate the role of these disulfide bonds in folding and assembly of the SOD apo protein (apoSOD) homodimer through extensive protein engineering. The results show that apoSOD folds in a simple three-state process by means of two kinetic barriers: 2D<==>2M<==>M(2). The early predominant barrier represents folding of the monomers (M), and the late barrier the assembly of the dimer (M(2)). Unique for this mechanism is a dependence of protein concentration on the unfolding

SUBMITTER: Lindberg MJ 

PROVIDER: S-EPMC528748 | biostudies-literature | 2004 Nov

REPOSITORIES: biostudies-literature