ArticleBiochemistry2011
Glutathionylation at Cys-111 induces dissociation of wild type and FALS mutant SOD1 dimers.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 94 citations in OpenAlex.
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- Novel extracellular vesicle release pathway facilitated by toxic superoxide dismutase 1 oligomers.Neurobiology of disease · 2026Article
- N-Truncated Superoxide Dismutase-1 in Cerebrospinal Fluid Is Folded and Active.Journal of neurochemistry · 2026Article
- Oxidative denaturation of Cu/Zn-superoxide dismutase associated with neurodegenerative diseases.Protein science : a publication of the Protein Society · 2025Article
- Pathological Disulfide Bond Crosslinking: Molecular Insights into Amyloidogenesis and Diseases Progression.Chembiochem : a European journal of chemical biology · 2025Review
- Trimeric superoxide dismutase 1 antibody as a universal biomarker for ALS.Research square · 2025Article
- Biophysical and spectroscopical insights into structural modulation of species in the aggregation pathway of superoxide dismutase 1.Communications chemistry · 2025Article
- Pathological Involvement of Protein Phase Separation and Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Mass spectrometry imaging of SOD1 protein-metal complexes in SOD1G93A transgenic mice implicates demetalation with pathology.Nature communications · 2024Article
- Oxidative Cysteine Post Translational Modifications Drive the Redox Code Underlying Neurodegeneration and Amyotrophic Lateral Sclerosis.Antioxidants (Basel, Switzerland) · 2024Review
- Engineering a monobody specific to monomeric Cu/Zn-superoxide dismutase associated with amyotrophic lateral sclerosis.Protein science : a publication of the Protein Society · 2024Article
- Big versus small: The impact of aggregate size in disease.Protein science : a publication of the Protein Society · 2023Review
- S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Altered SOD1 maturation and post-translational modification in amyotrophic lateral sclerosis spinal cord.Brain : a journal of neurology · 2022Article
- Toxic SOD1 trimers are off-pathway in the formation of amyloid-like fibrils in ALS.Biophysical journal · 2022Article
- Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.Chemical reviews · 2021Review
- Proteomic Approaches to Study Cysteine Oxidation: Applications in Neurodegenerative Diseases.Frontiers in molecular neuroscience · 2021Review
- When a foreign gene meets its native counterpart: computational biophysics analysis of two PgiC loci in the grass Festuca ovina.Scientific reports · 2020Article
- The impact of proteostasis dysfunction secondary to environmental and genetic causes on neurodegenerative diseases progression and potential therapeutic intervention.Environmental science and pollution research international · 2020Review
- Dysregulation of the glutaredoxin/American journal of physiology. Cell physiology · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mutation of the ubiquitous cytosolic enzyme Cu/Zn superoxide dismutase (SOD1) is hypothesized to cause familial amyotrophic lateral sclerosis (FALS) through structural destabilization leading to misfolding and aggregation. Considering the late onset of symptoms as well as the phenotypic variability among patients with identical SOD1 mutations, it is clear that nongenetic factor(s) impact ALS etiology and disease progression. Here we examine the effect of Cys-111 glutathionylation, a physiologically prevalent post-translational oxidative modification, on the stabilities of wild type SOD1 and two phenotypically diverse FALS mutants, A4V and I112T. Glutathionylation results in profound destabilization of SOD1(WT) dimers, increasing the equilibrium dissociation constant K(d) to ~10-20 μM, comparable to that of the aggressive A4V mutant. SOD1(A4V) is further destabilized by glutathionylation, experiencing an ~30-fold increase in K(d). Dissociation kinetics of glutathionylated SOD1(WT) and SOD1(A4V) are unchanged, as measured by surface plasmon resonance, indicating that glutathionylation destabilizes these variants by decreasing association rate. In contrast, SOD1(I112T) has a modestly increased dissociation rate but no change in K(d) when glutathionylated. Using computational structural modeling, we show that the distinct effects of glutathionylation on different SOD1 variants correspond to changes in composition of the dimer interface. Our experimental and computational results show that Cys-111 glutathionylation induces structural rearrangements that modulate stability of both wild type and FALS mutant SOD1. The distinct sensitivities of SOD1 variants to glutathionylation, a modification that acts in part as a coping mechanism for oxidative stress, suggest a novel mode by which redox regulation and aggregation propensity interact in ALS.
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