Glutathionylation potentiates benign superoxide dismutase 1 variants to the toxic forms associated with amyotrophic lateral sclerosis

Authors

Luke McAlary, University of WollongongFollow
Justin J. Yerbury, University of WollongongFollow
J. Andrew Aquilina, University of WollongongFollow

RIS ID

85284

Publication Details

McAlary, L., Yerbury, J. J. & Aquilina, J. (2013). Glutathionylation potentiates benign superoxide dismutase 1 variants to the toxic forms associated with amyotrophic lateral sclerosis. Scientific Reports, 3 3275-1-3275-6.

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 SOD1WT had disproportionately increased dissociation constants when glutathionylated. This defines a key role for glutathionylation in superoxide dismutase 1 associated familial amyotrophic lateral sclerosis.

Grant Number

NHMRC/1003032

Additional Grant Number

http://purl.org/au-research/grants/NHMRC/1003032