Artículo
Structural disorder of monomeric α-synuclein persists in mammalian cells
Theillet, Francois Xavier; Binolfi, Andrés
; Bekei, Beata; Martorana, Andrea; Rose, Honor May; Stuiver, Marchel; Verzini, Silvia; Lorenz, Dorothea; Van Rossum, Marleen; Goldfarb, Daniella; Selenko, Philipp
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
02/2016
Editorial:
Nature Publishing Group
Revista:
Nature
ISSN:
0028-0836
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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-β 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.
Palabras clave:
Alpha-Synuclein
,
In-Cell Nmr
,
Intrinsically Disordered Proteins
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Articulos(CCT - ROSARIO)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Citación
Theillet, Francois Xavier; Binolfi, Andrés; Bekei, Beata; Martorana, Andrea; Rose, Honor May; et al.; Structural disorder of monomeric α-synuclein persists in mammalian cells; Nature Publishing Group; Nature; 530; 7588; 2-2016; 45-50
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