F3‐02‐01: Structure and function of alpha‐synuclein

Alpha-synuclein is linked to both idiopathic and familial forms of Parkinson's and is found aggregated into amyloid fibrils in Lewy Bodies. Structural studies of alpha-synuclein in vitro have demonstrated that the protein is highly disordered when isolated in solution, yet retains some degree of transient secondary and tertiary structure. The importance of such transient structure in influencing synuclein aggregation has been much debated, and will be discussed in detail. Alpha-synuclein also binds to lipid-membranes in vivo and in vitro and adopts a highly helical structure upon doing so. We have shown that this helical structure can occur in the form of a single long helix, but can also transition to a conformation where the helix is broken into two shorter helices separated by a linker. The implications of these structures and their interconversion for the physiological function of alpha-synuclein will also be discussed.