Detection of Transient Interchain Interactions in the Intrinsically Disordered Protein α-Synuclein by NMR Paramagnetic Relaxation Enhancement

NMR paramagnetic relaxation enhancement experiments were applied to the intrinsically disordered protein alpha-synuclein, the primary protein in Parkinson's disease, to directly characterize transient intermolecular complexes at neutral and low pH. At neutral pH, we observed weak N- to C-terminal interchain contacts driven by electrostatic interactions, while at low pH, the C- to C-terminal interchain interactions are significantly stronger and driven by hydrophobic contacts. Characterization of these first interchain interactions will provide fundamental insight into the mechanism of amyloid formation.