Structural disorder of monomeric α-synuclein persists in mammalian cells.
Nature
; 530(7588): 45-50, 2016 Feb 04.
Article
en En
| MEDLINE
| ID: mdl-26808899
ABSTRACT
Intracellular aggregation of the human amyloid protein α-synuclein is causally linked to Parkinson's disease. While the isolated protein is intrinsically disordered, its native structure in mammalian cells is not known. Here we use nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy to derive atomic-resolution insights into the structure and dynamics of α-synuclein in different mammalian cell types. We show that the disordered nature of monomeric α-synuclein is stably preserved in non-neuronal and neuronal cells. Under physiological cell conditions, α-synuclein is amino-terminally acetylated and adopts conformations that are more compact than when in buffer, with residues of the aggregation-prone non-amyloid-ß component (NAC) region shielded from exposure to the cytoplasm, which presumably counteracts spontaneous aggregation. These results establish that different types of crowded intracellular environments do not inherently promote α-synuclein oligomerization and, more generally, that intrinsic structural disorder is sustainable in mammalian cells.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Espacio Intracelular
/
Alfa-Sinucleína
Límite:
Humans
Idioma:
En
Revista:
Nature
Año:
2016
Tipo del documento:
Article
País de afiliación:
Alemania