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|Titolo:||Nanoscale Imaging of Toxic Protein Aggregates|
|Autori interni:||SONCINI, MONICA|
CASARI, CARLO SPARTACO
REDAELLI, ALBERTO CESARE LUIGI
BOTTANI, CARLO ENRICO
|Data di pubblicazione:||2011|
|Abstract:||Protein misfolding underlies neurodegenerative disorders, for which no treatment is available. In particular, we present an investigation of misfolding process of Ataxin-3 (AT-3) whose misfolding is responsible of a neurodegenerative disease, named Spinocerebral Ataxia Type 3. Atomic force Microscopy (AFM) has been exploited with the aim of addressing a protein direct imaging at nanoscale level. A first analysis of folding process for several AT-3 variants was exploited to obtain kinetic folding model, depending on the length of the poly-Q chain. The misfolding process was then studied due to thermal treatments and to interaction with solid surface with different physical properties. In particular for the native domain (AT-3/182Δ), named Josephin domain (JD), both filaments of proteins and isolated globular structures on gold and silicon are detected, while only globular entities are observed on mica. Molecular Dynamics Simulations (MD) of isolated AT-3/182Δ were also performed considering the effect of hydrophobicity/hydrophilicity of the surface. We show that different conformations promote (on gold) or inhibit (on mica) the protein misfolding. These results suggest that the expanded poly-Q tract increases the probability of misfolding but the native domain itself acts as template in the misfolding pathway, when in contact with hydrophobic substrates.|
|Appare nelle tipologie:||04.1 Contributo in Atti di convegno|
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