Modulating the Folding Landscape of Superoxide Dismutase 1 with Targeted Molecular Binders
| Autor: | Beatriz Atsavapranee, David N. Bunck, David G. VanderVelde, James R. Heath, Anna Katrine Museth |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular 0301 basic medicine Protein Folding High-throughput screening SOD1 Molecular Conformation Peptide Ligands Peptides Cyclic 01 natural sciences Article Catalysis Superoxide dismutase 03 medical and health sciences Superoxide Dismutase-1 0302 clinical medicine medicine Native state Humans Amyotrophic lateral sclerosis chemistry.chemical_classification biology 010405 organic chemistry Chemistry Point mutation General Medicine General Chemistry medicine.disease 0104 chemical sciences Cell biology 030104 developmental biology biology.protein Protein folding 030217 neurology & neurosurgery |
| Popis: | Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is characterized by motor neuron death with average survival times of 2 ‐ 5 years. One cause of this disease is the misfolding of superoxide dismutase 1 (SOD1), a protein whose stability and aggregation propensity are affected by point mutations spanning the protein. Here, we use an epitope‐specific, high‐throughput screen to identify peptides that both stabilize the native conformation of SOD1 as well as accelerate its folding by 2.5‐fold. Ligands targeted to the electrostatic loop on the periphery of the protein tightened the non‐metalated structure and accelerated its folding. This strategy may be useful for fundamental studies of protein energy landscapes as well as designing new classes of therapeutics. |
| Databáze: | OpenAIRE |
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