ArticleProceedings of the National Academy of Sciences of the United States of America2013
SOD1 exhibits allosteric frustration to facilitate metal binding affinity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- Uncovering the molecular details of the 14-3-3 recruitment by mutant Sod1 species.Scientific reports · 2025Article
- Structure of a superoxide dismutase from a tardigrade: Ramazzottius varieornatus strain YOKOZUNA-1.Acta crystallographica. Section F, Structural biology communications · 2023Article
- 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
- Article
- Conformational dynamics of superoxide dismutase (SOD1) in osmolytes: a molecular dynamics simulation study.RSC advances · 2020Article
- Local frustration determines loop opening during the catalytic cycle of an oxidoreductase.eLife · 2020Article
- Successes and challenges in simulating the folding of large proteins.The Journal of biological chemistry · 2020Review
- Local frustration around enzyme active sites.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The Role of Metal Binding in the Amyotrophic Lateral Sclerosis-Related Aggregation of Copper-Zinc Superoxide Dismutase.Molecules (Basel, Switzerland) · 2017Review
- Incorporation of a Reporter Peptide in FPOP Compensates for Adventitious Scavengers and Permits Time-Dependent Measurements.Journal of the American Society for Mass Spectrometry · 2017Article
- As Simple As Possible, but Not Simpler: Exploring the Fidelity of Coarse-Grained Protein Models for Simulated Force Spectroscopy.PLoS computational biology · 2016Article
- A mechanism for propagated SOD1 misfolding from frustration analysis of a G85R mutant protein assembly.Biochemical and biophysical research communications · 2016Article
- Protein Frustratometer 2: a tool to localize energetic frustration in protein molecules, now with electrostatics.Nucleic acids research · 2016Article
- Omega-3 fatty acids differentially modulate enzymatic anti-oxidant systems in skeletal muscle cells.Cell stress & chaperones · 2016Article
- Insights into the role of the unusual disulfide bond in copper-zinc superoxide dismutase.The Journal of biological chemistry · 2015Article
- Insights into SOD1-linked amyotrophic lateral sclerosis from NMR studies of Ni(2+)- and other metal-ion-substituted wild-type copper-zinc superoxide dismutases.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2014Article
- Superoxide dismutases and superoxide reductases.Chemical reviews · 2014Review
- Mechanical resistance in unstructured proteins.Biophysical journal · 2013Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Superoxide dismutase-1 (SOD1) is a ubiquitous, Cu and Zn binding, free-radical defense enzyme whose misfolding and aggregation play a potential key role in amyotrophic lateral sclerosis, an invariably fatal neurodegenerative disease. Over 150 mutations in SOD1 have been identified with a familial form of the disease, but it is presently not clear what unifying features, if any, these mutants share to make them pathogenic. Here, we develop several unique computational assays for probing the thermo-mechanical properties of both ALS-associated and rationally designed SOD1 variants. Allosteric interaction-free energies between residues and metals are calculated, and a series of atomic force microscopy experiments are simulated with variable tether positions to quantify mechanical rigidity "fingerprints" for SOD1 variants. Mechanical fingerprinting studies of a series of C-terminally truncated mutants, along with an analysis of equilibrium dynamic fluctuations while varying native constraints, potential energy change upon mutation, frustratometer analysis, and analysis of the coupling between local frustration and metal binding interactions for a glycine scan of 90 residues together, reveal that the apo protein is internally frustrated, that these internal stresses are partially relieved by mutation but at the expense of metal-binding affinity, and that the frustration of a residue is directly related to its role in binding metals. This evidence points to apo SOD1 as a strained intermediate with "self-allostery" for high metal-binding affinity. Thus, the prerequisites for the function of SOD1 as an antioxidant compete with apo state thermo-mechanical stability, increasing the susceptibility of the protein to misfold in the apo state.
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