SOD1 gains pro-oxidant activity upon aberrant oligomerization: change in enzymatic activity by intramolecular disulfide bond cleavage.

ABSTRACT: Copper-zinc superoxide dismutase (SOD1) has been proposed as one of the causative proteins of amyotrophic lateral sclerosis (ALS). The accumulation of non-native conformers, oligomers, and aggregates of SOD1 in motor neurons is considered responsible for this disease. However, it remains unclear which specific feature of these species induces the onset of ALS. In this study, we showed that disulfide-linked oligomers of denatured SOD1 exhibit pro-oxidant activity. Substituting all the cysteine residues in the free thiol state with serine resulted in the loss of both the propensity to oligomerize and the increase in pro-oxidant activity after denaturation. In contrast, these cysteine mutants oligomerized and acquired the pro-oxidant activity after denaturation in the presence of a reductant

SUBMITTER: Yamazaki K 

PROVIDER: S-EPMC9273606 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature