Structural Properties of Pore-Forming Oligomers of alpha-Synuclein

HAI-YOUNG KIM, MIN-KYU CHO, ASHUTOSH KUMAR, ELKE MAIER, CARSTEN SIEBENHAAR, STEFAN BECKER, CLAUDIO O. FERNANDEZ,HILAL A. LASHUEL, ROLAND BENZ,ADAM LANGE,AND MARKUS ZWECKSTETTER

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

AMER CHEMICAL SOC

Año: 2009 vol. 131 p. 17482 - 17489

0002-7863

Soluble oligomers are potent toxins in many neurodegenerative diseases, but little is knownabout 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 structure differs from that of amyloid fibrils of alpha-synuclein.