ArticleThe Journal of biological chemistry2015
The Disulfide Bond, but Not Zinc or Dimerization, Controls Initiation and Seeded Growth in Amyotrophic Lateral Sclerosis-linked Cu,Zn Superoxide Dismutase (SOD1) Fibrillation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 63 citations in OpenAlex.
- Diverse effects of coexpression of human SOD1 variants on motor neuron disease.Human molecular genetics · 2025Article
- Impact of cysteine mutations on the structural dynamics and functional impairment of SOD1: insights into the pathogenicity of amyotrophic lateral sclerosis.Genomics & informatics · 2025Article
- Structural insights into the role of reduced cysteine residues in SOD1 amyloid filament formation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Implications of ALS-Associated Mutations on Biochemical and Biophysical Features of hSOD1 and Aggregation Formation.Biochemical genetics · 2024Article
- Structural analysis of the overoxidized Cu/Zn-superoxide dismutase in ROS-induced ALS filament formation.Communications biology · 2022Article
- Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion.Nature communications · 2022Article
- Biochemical Analysis ofACS infectious diseases · 2022Article
- Novel chemical inhibitor against SOD1 misfolding and aggregation protects neuron-loss and ameliorates disease symptoms in ALS mouse model.Communications biology · 2021Article
- Variation in the vulnerability of mice expressing human superoxide dismutase 1 to prion-like seeding: a study of the influence of primary amino acid sequence.Acta neuropathologica communications · 2021Article
- A Metal-Free, Disulfide Oxidized Form of Superoxide Dismutase 1 as a Primary Misfolded Species with Prion-Like Properties in the Extracellular Environments Surrounding Motor Neuron-Like Cells.International journal of molecular sciences · 2021Article
- Novel SOD1 monoclonal antibodies against the electrostatic loop preferentially detect misfolded SOD1 aggregates.Neuroscience letters · 2021Article
- Regulation of Functional Protein Aggregation by Multiple Factors: Implications for the Amyloidogenic Behavior of the CAP Superfamily Proteins.International journal of molecular sciences · 2020Review
- Molecular and Cellular Mechanisms Affected in ALS.Journal of personalized medicine · 2020Review
- Pro-Oxidant Activity of an ALS-Linked SOD1 Mutant in Zn-Deficient Form.Molecules (Basel, Switzerland) · 2020Article
- A Novel SOD1 Intermediate Oligomer, Role of Free Thiols and Disulfide Exchange.Frontiers in neuroscience · 2020Article
- Tryptophan residue 32 in human Cu-Zn superoxide dismutase modulates prion-like propagation and strain selection.PloS one · 2020Article
- Amyotrophic Lateral Sclerosis: Proteins, Proteostasis, Prions, and Promises.Frontiers in cellular neuroscience · 2020Article
- Metal ions and redox balance regulate distinct amyloid-like aggregation pathways of GAPR-1.Scientific reports · 2019Article
- Nonnative structure in a peptide model of the unfolded state of superoxide dismutase 1 (SOD1): Implications for ALS-linked aggregation.The Journal of biological chemistry · 2019Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Aggregation of copper-zinc superoxide dismutase (SOD1) is a defining feature of familial ALS caused by inherited mutations in the sod1 gene, and misfolded and aggregated forms of wild-type SOD1 are found in both sporadic and familial ALS cases. Mature SOD1 owes its exceptional stability to a number of post-translational modifications as follows: formation of the intramolecular disulfide bond, binding of copper and zinc, and dimerization. Loss of stability due to the failure to acquire one or more of these modifications is proposed to lead to aggregation in vivo. Previously, we showed that the presence of apo-, disulfide-reduced SOD1, the most immature form of SOD1, results in initiation of fibrillation of more mature forms that have an intact Cys-57-Cys-146 disulfide bond and are partially metallated. In this study, we examine the ability of each of the above post-translational modifications to modulate fibril initiation and seeded growth. Cobalt or zinc binding, despite conferring great structural stability, neither inhibits the initiation propensity of disulfide-reduced SOD1 nor consistently protects disulfide-oxidized SOD1 from being recruited into growing fibrils across wild-type and a number of ALS mutants. In contrast, reduction of the disulfide bond, known to be necessary for fibril initiation, also allows for faster recruitment during seeded amyloid growth. These results identify separate factors that differently influence seeded growth and initiation and indicate a lack of correlation between the overall thermodynamic stability of partially mature SOD1 states and their ability to initiate fibrillation or be recruited by a growing fibril.
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