Point mutations affecting yeast prion propagation change the structure of its amyloid fibrils
| Autor: | Mikhail V. Belousov, Irina M. Kuznetsova, Nina P. Trubitsina, Anna I. Sulatskaya, Galina A. Zhouravleva, Maksim I. Sulatsky, Konstantin K. Turoverov, Manuel A. Llanos, Stanislav A. Bondarev, Andrey V. Kajava |
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| Přispěvatelé: | Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1) |
| Rok vydání: | 2020 |
| Předmět: |
Amyloid
Biología macromolecular substances 02 engineering and technology Protein aggregation 010402 general chemistry Fibril Betaserpentine 01 natural sciences Turn (biochemistry) chemistry.chemical_compound structural polymorphism amyloid fibril Materials Chemistry [PSI+] prion [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology super-pleated beta-structure Physical and Theoretical Chemistry Super-pleated beta-structure Spectroscopy chemistry.chemical_classification Oligopeptide Point mutation thioflavin T equilibrium microdialysis Binding stoichiometry binding stoichiometry 021001 nanoscience & nanotechnology Condensed Matter Physics Atomic and Molecular Physics and Optics 0104 chemical sciences Electronic Optical and Magnetic Materials Amino acid betaserpentine chemistry Sup35p Thioflavin T Biophysics Thioflavin point mutation 0210 nano-technology Amyloid fibril Structural polymorphism Equilibrium microdialysis |
| Zdroj: | Journal of Molecular Liquids Journal of Molecular Liquids, Elsevier, 2020, 314, pp.113618. ⟨10.1016/j.molliq.2020.113618⟩ SEDICI (UNLP) Universidad Nacional de La Plata instacron:UNLP |
| ISSN: | 0167-7322 |
| DOI: | 10.1016/j.molliq.2020.113618 |
| Popis: | We investigated the effect of the point substitutions in the N-terminal domain of the yeast prion protein Sup35 (Sup35NMp) on the structure of its amyloid fibrils. As the objects of the study, proteins with mutations that have different influence on the [PSI+] prion propagation, but do not prevent the aggregation of Sup35NMp in vitro were chosen. The use of the wide range of physico-chemical methods allowed us to show significant differences in the structure of these aggregates, their physical size, clumping tendency. Also we demonstrated that the fluorescent probe thioflavin T (ThT) can be successfully used for investigation of subtle changes in the structural organization of fibrils formed from various Sup35NMp. The obtained results and our theoretical predictions allowed us to conclude that some of selected amino acid substitutions delimit the region of the protein that forms the core of amyloid fibrils, and change the fibrils structure. The relationship of structural features of in vitro Sup35NMp amyloid aggregates with the stability of the [PSI+] prion in vivo allowed us to suggest that oligopeptide repeats (R) of the amyloidogenic N-terminal domain of Sup35NMp from R0 to R2 play a key role in protein aggregation. Their arrangement rather than just presence is critical for propagation of the strong [PSI+] prion variants. The results confirm the suitability of the proposed combination of theoretical and empirical approaches for identifying changes in the amyloid fibrils structure, which, in turn, can significantly affect both the functional stability of amyloid fibrils and their pathogenicity. Laboratorio de Investigación y Desarrollo de Bioactivos |
| Databáze: | OpenAIRE |
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