title: Glutathionylation potentiates benign superoxide dismutase 1 variants to the toxic forms associated with amyotrophic lateral sclerosis.
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.
authors.affiliation: 1] 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.
authors.forename: Luke
authors.initials: L
authors.lastname: McAlary
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Yerbury
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Aquilina
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D011994:Recombinant Proteins; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione