Format

Send to

Choose Destination
Nature. 2016 Feb 4;530(7588):45-50. doi: 10.1038/nature16531. Epub 2016 Jan 25.

Structural disorder of monomeric α-synuclein persists in mammalian cells.

Author information

1
In-Cell NMR Laboratory, Department of NMR-supported Structural Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rössle Strasse 10, 13125 Berlin, Germany.
2
Department of Chemical Physics, Weizmann Institute of Science, Rehovot 76100, Israel.
3
Department of Molecular Physiology and Cell Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rössle Strasse 10, 13125 Berlin, Germany.

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-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.

PMID:
26808899
DOI:
10.1038/nature16531
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center