Tracking SOD1 heterodimerization processes using fluorescence aggregation

Copper-zinc superoxide dismutase (CuZnSOD) is an enzyme which is found throughout eukaryotic cells and in some areas of bacterial cells and is responsible for catalyzing the transformation of superoxides into hydrogen peroxide and dioxygen. Studies have found that inherited mutations in the gene encoding CuZnSOD, SOD1, are present in a portion of cases of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease marked by motor neuron degeneration and cell death. Because of this, CuZnSOD is a well-studied protein, though much is still to be learned about the pathology of the disease and how SOD1 causes it. One such aspect of disease pathology that is yet to be explored fully is the role subunit exchange plays in protein aggregation. Many of familial ALS-causing mutations are autosomal dominant, meaning interactions between wild-type (WT) and mutant forms of SOD1 protein exist. Heterodimers, containing one WT subunit and one mutant subunit, have been observed in tissue samples of individuals affected by ALS, necessitating study of the process by which these heterodimers are formed. In order to study these properties of subunit exchange and heterodimerization, recent studies have used fluorescence aggregation assays in order to monitor formation of protein aggregates over time and study the types of conditions that result in heterodimerization of SOD1 protein. By tracking the kinetics of heterodimerization over time, much can be learned from the rate and products formed from this reaction. These fluorescence assays are a unique way of studying protein aggregation kinetics, and the findings indicate varying rates of aggregation according to certain mutations in SOD1. The findings from this set of research using aggregation assays serves as a launching point for understanding how the presence of both WT and mutant protein may affect or accelerate disease progression as a result of heterodimerization.