Alpha-Synuclein Disease Mutations Are Structurally Defective and Locally Affect Membrane Binding.

The intrinsically disordered human protein alpha-Synuclein (S) has a prominent role in Parkinson's disease (PD) pathology. Several familial variants of S are correlated with inherited PD. Disease mutations have been shown to have an impact on lipid membrane binding. Here, using electron paramagnetic resonance spectroscopy in combination with site-directed spin labeling, we show that familial PD-associated variants are structurally defective in membrane binding and alter the local binding properties of the protein. [ABSTRACT FROM AUTHOR]