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| Content Provider | Springer Nature Link |
|---|---|
| Author | Healy, Eamonn F. Cervantes, Luis |
| Copyright Year | 2016 |
| Abstract | Superoxide dismutase [Cu–Zn], or SOD1, is a homo-dimeric protein that functions as an antioxidant by scavenging for superoxides. A wide range of SOD1 variants are linked to inherited, or familial, amyotrophic lateral sclerosis, a progressive and fatal neurodegenerative disease. Aberrant SOD1 oligomerization has been strongly implicated in disease causation, even for sporadic ALS, or SALS, which accounts for ~90 % of ALS cases. Small heat shock proteins (sHSP) have been shown to protect against amyloid fibril formation in vitro, and the sHSP αB-crystallin suppresses in vitro aggregation of SOD1. We are seeking to elucidate the structural features of both SOD1 amyloid formation and αB-crystallin amyloid suppression. Specifically, we have used a flexible docking protocol to refine our model of a SOD1 non-obligate tetramer, postulated to function as a transient desolvating complex. Homology modeling and molecular dynamics (MD) are used to supply the missing structural elements of a previously characterized SOD1 amyloid filament, thereby providing a structural analysis for the observed gain of interaction. This completed filament is then further modified using MD to provide a structural model for protofibril capping of SOD1 filaments by αB-crystallin. |
| Starting Page | 853 |
| Ending Page | 859 |
| Page Count | 7 |
| File Format | |
| ISSN | 01757571 |
| Journal | European Biophysics Journal |
| Volume Number | 45 |
| Issue Number | 8 |
| e-ISSN | 14321017 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2016-08-05 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Superoxide dismutase Amyotrophic lateral sclerosis Electrostatic loop αB-crystallin Biochemistry Biological and Medical Physics, Biophysics Cell Biology Neurobiology Membrane Biology Nanotechnology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Biophysics |
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