title: A mechanism for propagated SOD1 misfolding from frustration analysis of a G85R mutant protein assembly.
abstract: Application of landscape theory and the dehydron hypothesis to a crystal structure of a G85R mutant superoxide dismutase (SOD1) tetrameric complex allows for the description of a prion-like hypothesis that serves to explain propagated SOD1 misfolding. We have developed two conformational-change scenarios, one local to the ESL at the complex interface, and a second displacement at the ESL of the otherdimeric subunit. When taken together these provide for a prion-like mechanism that can serve to explain the observed conversion of wtSOD1 to a misfolded form by the G85R mutant.
authors: Department of Chemistry, St. Edward's University, Austin, TX 78704, USA. Electronic address: healy@stedwards.edu.
authors: Eamonn F
authors: EF
authors: Healy
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D050505:Mutant Proteins / Q000737:chemistry* / Q000378:metabolism; D020125:Mutation, Missense; D011328:Prions / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D000072105:Superoxide Dismutase-1 / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D011328:Prions; D021122:Protein Subunits; C000606290:SOD1 protein, human; D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis; Dehydrons; Electrostatic loop; Frustration contacts; G85R SOD1 mutant; Superoxide dismutase