Alteration of the α‐Synuclein Folding Landscape by a Mutation Related to Parkinson’s Disease

Shape shifting linked to disease: A single-molecule fluorescence technique was used to probe structures of an intrinsically disordered brain protein. A mutation was found to tilt the coupled binding–folding energy landscape of the protein and inhibited switching between induced ordered structures (see picture). The observations provide fundamental insight into the molecular basis of Parkinson's disease.