title: Temperature profoundly affects ataxin-3 fibrillogenesis.
abstract: Ataxin-3 (AT3) triggers spinocerebellar ataxia type 3 when it carries a polyglutamine stretch expanded beyond a critical threshold. By Fourier transform infrared spectroscopy and atomic force microscopy we previously showed that a normal (AT3Q24) and an expanded (AT3Q55) variant were capable of evolving into oligomers and protofibrils at 37 °C, whereas only the expanded form generated irreversibly aggregated fibrils that also were associated with a network of side-chain glutamine hydrogen bonding [Natalello et al. (2011) PLoS One. 6:e18789]. We report here that AT3Q24, when gradually heated up to 85 °C, undergoes aggregation similar to that observed at 37 °C; in contrast, AT3Q55 only generates large, amorphous aggregates. We propose a possible interpretation of the mechanism by which temperature affects the outcome of fibrillogenesis.
authors.affiliation: Department of Energy and NEMAS, Center for NanoEngineered Materials and Surfaces, Politecnico di Milano, via Ponzio 34/3 I-20133 Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Apicella
authors.forename: Antonino
authors.initials: A
authors.lastname: Natalello
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Frana
authors.forename: Andrea
authors.initials: A
authors.lastname: Baserga
authors.forename: Carlo Spartaco
authors.initials: CS
authors.lastname: Casari
authors.forename: Carlo Enrico
authors.initials: CE
authors.lastname: Bottani
authors.forename: Silvia Maria
authors.initials: SM
authors.lastname: Doglia
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortora
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Regonesi
mesh_terms: D019943:Amino Acid Substitution; D058227:Amyloidogenic Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D000067699:Ataxin-3; D006801:Humans; D018625:Microscopy, Atomic Force; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D058227:Amyloidogenic Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3