ArticleProtein science : a publication of the Protein Society2015
Destabilization of the dimer interface is a common consequence of diverse ALS-associated mutations in metal free SOD1.
Article in Protein science : a publication of the Protein Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 49 citations in OpenAlex.
- Surface electrostatic networks control hydrophobic core remodeling in a pH-dependent switching protein.bioRxiv : the preprint server for biology · 2026Article
- Structures of DnaA domain I reveal a dimer conserved across Actinomycetes.Nucleic acids research · 2026Article
- Tracking Protein Misfolding and Oligomerization: A Temperature-Controlled Ion Mobility-Mass Spectrometry Approach.Analytical chemistry · 2026Article
- The HDAC Inhibitor Butyrate Reduces SOD1 Aggregation and Improves Motor Function inInternational journal of cell biology · 2026Article
- Theoretical evaluation of a bulkyRSC advances · 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
- Mass spectrometry methods and mathematical PK/PD model for decision tree-guided covalent drug development.Nature communications · 2025Article
- Rapidly Progressing and Early-Onset Forms of Amyotrophic Lateral Sclerosis Caused by a NovelNeurology. Genetics · 2024Article
- Direct observation of prion-like propagation of protein misfolding templated by pathogenic mutants.Nature chemical biology · 2024Article
- Review
- First Principles Calculation of Protein-Protein Dimer Affinities of ALS-Associated SOD1 Mutants.Frontiers in molecular biosciences · 2022Article
- Free energy calculations of ALS-causing SOD1 mutants reveal common perturbations to stability and dynamics along the maturation pathway.Protein science : a publication of the Protein Society · 2021Article
- Superoxide Dismutase 1 in Health and Disease: How a Frontline Antioxidant Becomes Neurotoxic.Angewandte Chemie (International ed. in English) · 2021Review
- Trifluoroethanol Partially Unfolds G93A SOD1 Leading to Protein Aggregation: A Study by Native Mass Spectrometry and FPOP Protein Footprinting.Biochemistry · 2020Article
- TNF receptor-associated factor 6 interacts with ALS-linked misfolded superoxide dismutase 1 and promotes aggregation.The Journal of biological chemistry · 2020Article
- T54R mutation destabilizes the dimer of superoxide dismutase 1RSC advances · 2020Article
- Amyotrophic Lateral Sclerosis: Proteins, Proteostasis, Prions, and Promises.Frontiers in cellular neuroscience · 2020Article
- Implications of fALS Mutations on Sod1 Function and Oligomerization in Cell Models.Molecular neurobiology · 2018Article
- Effects of maturation on the conformational free-energy landscape of SOD1.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Computing disease-linked SOD1 mutations: deciphering protein stability and patient-phenotype relations.Scientific reports · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
Neurotoxic misfolding of Cu, Zn-superoxide dismutase (SOD1) is implicated in causing amyotrophic lateral sclerosis, a devastating and incurable neurodegenerative disease. Disease-linked mutations in SOD1 have been proposed to promote misfolding and aggregation by decreasing protein stability and increasing the proportion of less folded forms of the protein. Here we report direct measurement of the thermodynamic effects of chemically and structurally diverse mutations on the stability of the dimer interface for metal free (apo) SOD1 using isothermal titration calorimetry and size exclusion chromatography. Remarkably, all mutations studied, even ones distant from the dimer interface, decrease interface stability, and increase the population of monomeric SOD1. We interpret the thermodynamic data to mean that substantial structural perturbations accompany dimer dissociation, resulting in the formation of poorly packed and malleable dissociated monomers. These findings provide key information for understanding the mechanisms and energetics underlying normal maturation of SOD1, as well as toxic SOD1 misfolding pathways associated with disease. Furthermore, accurate prediction of protein-protein association remains very difficult, especially when large structural changes are involved in the process, and our findings provide a quantitative set of data for such cases, to improve modelling of protein association.
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