title: A hydrophobic gold surface triggers misfolding and aggregation of the amyloidogenic Josephin domain in monomeric form, while leaving the oligomers unaffected.
abstract: Protein misfolding and aggregation in intracellular and extracellular spaces is regarded as a main marker of the presence of degenerative disorders such as amyloidoses. To elucidate the mechanisms of protein misfolding, the interaction of proteins with inorganic surfaces is of particular relevance, since surfaces displaying different wettability properties may represent model systems of the cell membrane. Here, we unveil the role of surface hydrophobicity/hydrophilicity in the misfolding of the Josephin domain (JD), a globular-shaped domain of ataxin-3, the protein responsible for the spinocerebellar ataxia type 3. By means of a combined experimental and theoretical approach based on atomic force microscopy, Fourier transform infrared spectroscopy and molecular dynamics simulations, we reveal changes in JD morphology and secondary structure elicited by the interaction with the hydrophobic gold substrate, but not by the hydrophilic mica. Our results demonstrate that the interaction with the gold surface triggers misfolding of the JD when it is in native-like configuration, while no structural modification is observed after the protein has undergone oligomerization. This raises the possibility that biological membranes would be unable to affect amyloid oligomeric structures and toxicity.
authors.affiliation: Energy Department and NEMAS - Center for NanoEngineered Materials and Surfaces, Politecnico di Milano, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Apicella
authors.forename: Monica
authors.initials: M
authors.lastname: Soncini
authors.forename: Marco Agostino
authors.initials: MA
authors.lastname: Deriu
authors.forename: Antonino
authors.initials: A
authors.lastname: Natalello
authors.forename: Marcella
authors.initials: M
authors.lastname: Bonanomi
authors.forename: David
authors.initials: D
authors.lastname: Dellasega
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortora
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Regonesi
authors.forename: Carlo Spartaco
authors.initials: CS
authors.lastname: Casari
mesh_terms: D000042:Absorption; D000538:Aluminum Silicates / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011506:Proteins / Q000737:chemistry*; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties
chemical_list: D000538:Aluminum Silicates; D011506:Proteins; D012996:Solutions; D006046:Gold; C011934:mica