Alpha-synuclein pore forming activity upon membrane association

► Monomeric alpha-synuclein causes bursts of conductance in Planar Lipid Membranes. ► Three levels of sequentially related conductance levels were identified. ► Covalently bound alpha-synuclein dimers allow to explore relative orientation of the monomers in the pore. ► Alpha-synuclein forms barrel stave pores with the progressive insertion of four helical units. ► A model of pore formation accounting for the conductance levels is proposed.