Metal-free superoxide dismutase forms soluble oligomers under physiological conditions: a possible general mechanism for familial ALS.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder selectively affecting motor neurons; 90% of the total cases are sporadic, but 2% are associated with mutations in the gene coding for the antioxidant enzyme copper-zinc superoxide dismutase (SOD1). The causes of motor neuron death in ALS are poorly understood in general, but for SOD1-linked familial ALS, aberrant oligomerization of SOD1 mutant proteins has been strongly implicated. In this work, we show that wild-type human SOD1, when lacking both its metal ions, forms large, stable, soluble protein oligomers with an average molecular mass of approximately 650 kDa under physiological conditions, i.e., 37 degrees C, pH 7.0, and 100 microM protein concentration. It further is shown here that intermolecular disulf

SUBMITTER: Banci L 

PROVIDER: S-EPMC1899188 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature