Alpha-synuclein binds large unilamellar vesicles as an extended helix.

Interactions between the synaptic protein alpha-Synuclein and cellular membranes may be relevant both to its native function as well as its role in Parkinson's disease. We use single molecule Forster resonance energy transfer to probe the structure of alpha-Synuclein bound to detergent micelles and lipid vesicles. We find evidence that it forms a bent-helix when bound to highly curved detergent micelles, whereas it binds more physiological 100 nm diameter lipid vesicles as an elongated helix. Our results highlight the influence of membrane curvature in determining alpha-Synuclein conformation, which may be important for both its normal and disease-associated functions.