ArticlePLoS biology2019
Molecular recognition and maturation of SOD1 by its evolutionarily destabilised cognate chaperone hCCS.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases.MedComm · 2026Review
- From hemocuprein to CSRP: the many faces of Cu/Zn superoxide dismutase.Metallomics : integrated biometal science · 2026Review
- Landscapes of missense variant impact for human superoxide dismutase 1.American journal of human genetics · 2025Article
- Distinct amyloid fibril structures formed by ALS-causing SOD1 mutants G93A and D101N.EMBO reports · 2025Article
- Cuproptosis: a novel therapeutic mechanism in lung cancer.Cancer cell international · 2025Review
- 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
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Amyloid fibril structures and ferroptosis activation induced by ALS-causing SOD1 mutations.Science advances · 2024Article
- Implications of ALS-Associated Mutations on Biochemical and Biophysical Features of hSOD1 and Aggregation Formation.Biochemical genetics · 2024Article
- Atomic resolution map of the solvent interactions driving SOD1 unfolding in CAPRIN1 condensates.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pathogenic RBiochemistry · 2024Article
- Small molecules targeting different cellular pathologies for the treatment of amyotrophic lateral sclerosis.Medicinal research reviews · 2023Review
- Characterization of a novel cysteine-less Cu/Zn-superoxide dismutase in Paenibacillus lautus missing a conserved disulfide bond.The Journal of biological chemistry · 2023Article
- Evidence and Metabolic Implications for a New Non-Canonical Role of Cu-Zn Superoxide Dismutase.International journal of molecular sciences · 2023Article
- Structural analysis of the overoxidized Cu/Zn-superoxide dismutase in ROS-induced ALS filament formation.Communications biology · 2022Article
- A pathological link between dysregulated copper binding in Cu/Zn-superoxide dismutase and amyotrophic lateral sclerosis.Journal of clinical biochemistry and nutrition · 2022Article
- Article
- Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion.Nature communications · 2022Article
- Review
- Copper delivery to an endospore coat protein ofFrontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Superoxide dismutase-1 (SOD1) maturation comprises a string of posttranslational modifications which transform the nascent peptide into a stable and active enzyme. The successive folding, metal ion binding, and disulphide acquisition steps in this pathway can be catalysed through a direct interaction with the copper chaperone for SOD1 (CCS). This process confers enzymatic activity and reduces access to noncanonical, aggregation-prone states. Here, we present the functional mechanisms of human copper chaperone for SOD1 (hCCS)-catalysed SOD1 activation based on crystal structures of reaction precursors, intermediates, and products. Molecular recognition of immature SOD1 by hCCS is driven by several interface interactions, which provide an extended surface upon which SOD1 folds. Induced-fit complexation is reliant on the structural plasticity of the immature SOD1 disulphide sub-loop, a characteristic which contributes to misfolding and aggregation in neurodegenerative disease. Complexation specifically stabilises the SOD1 disulphide sub-loop, priming it and the active site for copper transfer, while delaying disulphide formation and complex dissociation. Critically, a single destabilising amino acid substitution within the hCCS interface reduces hCCS homodimer affinity, creating a pool of hCCS available to interact with immature SOD1. hCCS substrate specificity, segregation between solvent and biological membranes, and interaction transience are direct results of this substitution. In this way, hCCS-catalysed SOD1 maturation is finessed to minimise copper wastage and reduce production of potentially toxic SOD1 species.
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Registered trials
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