ArticleThe Journal of biological chemistry2011
Cutting off functional loops from homodimeric enzyme superoxide dismutase 1 (SOD1) leaves monomeric β-barrels.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Neurological Diseases can be Regulated by Phase Separation.Reviews of physiology, biochemistry and pharmacology · 2025Review
- Superoxide Dismutase 1 Folding Stability as a Target for Molecular Tweezers in SOD1-Related Amyotrophic Lateral Sclerosis.Chembiochem : a European journal of chemical biology · 2022Article
- A Short Tale of the Origin of Proteins and Ribosome Evolution.Microorganisms · 2022Review
- Structural analysis of the overoxidized Cu/Zn-superoxide dismutase in ROS-induced ALS filament formation.Communications biology · 2022Article
- Computational Insights into the Unfolding of a Destabilized Superoxide Dismutase 1 Mutant.Biology · 2021Article
- Polyanions Cause Protein Destabilization Similar to That in Live Cells.Biochemistry · 2021Article
- Connecting Longitudinal and Transverse Relaxation Rates in Live-Cell NMR.The journal of physical chemistry. B · 2020Article
- Diffusive protein interactions in human versus bacterial cells.Current research in structural biology · 2020Article
- Obtaining Hydrodynamic Radii of Intrinsically Disordered Protein Ensembles by Pulsed Field Gradient NMR Measurements.Methods in molecular biology (Clifton, N.J.) · 2020Article
- 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
- Effects of protein size, thermodynamic stability, and net charge on cotranslational folding on the ribosome.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Real-Time Observation of the Interaction between Thioflavin T and an Amyloid Protein by Using High-Sensitivity Rheo-NMR.International journal of molecular sciences · 2017Article
- Computing disease-linked SOD1 mutations: deciphering protein stability and patient-phenotype relations.Scientific reports · 2017Article
- Physicochemical code for quinary protein interactions inProceedings of the National Academy of Sciences of the United States of America · 2017Article
- As Simple As Possible, but Not Simpler: Exploring the Fidelity of Coarse-Grained Protein Models for Simulated Force Spectroscopy.PLoS computational biology · 2016Article
- Thermodynamics of protein destabilization in live cells.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- SOD1 aggregation in ALS mice shows simplistic test tube behavior.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Novel microscale approaches for easy, rapid determination of protein stability in academic and commercial settings.Biochimica et biophysica acta · 2014Article
- Identification of a misfolded region in superoxide dismutase 1 that is exposed in amyotrophic lateral sclerosis.The Journal of biological chemistry · 2014Article
- Solid-state NMR studies of metal-free SOD1 fibrillar structures.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2014Article
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4 authors.
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Abstract
Demetallation of the homodimeric enzyme Cu/Zn-superoxide dismutase (SOD1) is known to unleash pronounced dynamic motions in the long active-site loops that comprise almost a third of the folded structure. The resulting apo species, which shows increased propensity to aggregate, stands out as the prime disease precursor in amyotrophic lateral sclerosis (ALS). Even so, the detailed structural properties of the apoSOD1 framework have remained elusive and controversial. In this study, we examine the structural interplay between the central apoSOD1 barrel and the active-site loops by simply cutting them off; loops IV and VII were substituted with short Gly-Ala-Gly linkers. The results show that loop removal breaks the dimer interface and leads to soluble, monomeric β-barrels with high structural integrity. NMR-detected nuclear Overhauser effects are found between all of the constituent β-strands, confirming ordered interactions across the whole barrel. Moreover, the breathing motions of the SOD1 barrel are overall insensitive to loop removal and yield hydrogen/deuterium protection factors typical for cooperatively folded proteins (i.e. the active-site loops act as a "bolt-on" domain with little dynamic influence on its structural foundation). The sole exceptions are the relatively low protection factors in β-strand 5 and the turn around Gly-93, a hot spot for ALS-provoking mutations, which decrease even further upon loop removal. Taken together, these data suggest that the cytotoxic function of apoSOD1 does not emerge from its folded ground state but from a high energy intermediate or even from the denatured ensemble.
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