• Open Access

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


  • We thank Dr. Yann Gambin, and Dr. Jeffrey W. Kelly and co-workers for technical assistance, and Dr. Peter E. Wright for use of the CD spectrometer. The wild-type α-synuclein plasmid construct was a generous gift from Dr. Robert L. Nussbaum (National Institutes of Health, Bethesda). This research was supported by grant RO1 GM066833 from the National Institute of General Medical Sciences, NIH to A.A.D., and postdoctoral fellowships from the National Institute of Neurological Disorders and Stroke, NIH (A.C.M.F.) and the Leukemia and Lymphoma Society (J.C.F.).


original image

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.