Structural properties of pore-forming oligomers of alpha-synuclein.
Soluble oligomers are potent toxins in many neurodegenerative diseases, but little is known about the structure of soluble oligomers and their structure-toxicity relationship. Here we prepared on-pathway oligomers of the 140-residue protein alpha-synuclein, a key player in Parkinson's disease, at concentrations an order of magnitude higher than previously possible. The oligomers form ion channels with well-defined conductance states in a variety of membranes, and their beta-structure differs from that of amyloid fibrils of alpha-synuclein.
Kim
Hai-Young
HY
Department of NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Cho
Min-Kyu
MK
Kumar
Ashutosh
A
Maier
Elke
E
Siebenhaar
Carsten
C
Becker
Stefan
S
Fernandez
Claudio O
CO
Lashuel
Hilal A
HA
Benz
Roland
R
Lange
Adam
A
Zweckstetter
Markus
M
D001704:Biopolymers / Q000737:chemistry*; D015153:Blotting, Western; D018625:Microscopy, Atomic Force; D019906:Nuclear Magnetic Resonance, Biomolecular; D051844:alpha-Synuclein / Q000737:chemistry*
D001704:Biopolymers; D051844:alpha-Synuclein