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Glutathionylation potentiates benign superoxide dismutase 1 variants to the toxic forms associated with amyotrophic
Luke McAlary1, Justin J Yerbury, J Andrew Aquilina
11] Illawarra Health and Medical Research Institute, Northfields Avenue, Wollongong NSW, Australia 2522 [2] School of Biological Sciences, University of Wollongong, Northfields Avenue, Wollongong NSW, Australia 2522.
Abstract:
Dissociation of superoxide dismutase 1 dimers is enhanced by glutathionylation, although the dissociation constants reported to date are imprecise. We have quantified the discreet dissociation constants for wild-type superoxide dismutase 1 and six naturally occurring sequence variants, in their unmodified and glutathionylated forms, at the ratios expressed. Unmodified superoxide dismutase 1 variants that shared similar dissociation constants with SOD1(WT) had disproportionately increased dissociation constants when glutathionylated. This defines a key role for glutathionylation in superoxide dismutase 1 associated familial amyotrophic lateral sclerosis.
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