Structural characterization of pseudorepeat shuffled alpha-synuclein

Restricted until 27 June 2010. The 140-residue alpha-synuclein plays a central role in the molecular chain of events leading to Parkinson' s disease. Alpha-synuclein is dynamically unstructured in aqueous solution, but readily binds to negatively charged membranes and micelles. Seven degenerate 11-residue repeats located within the first 89 amino acid residues confer membrane binding in an alpha-helical conformation. In this research, the structure of a pseudorepeat shuffled alpha-synuclein variant is characterized by NMR spectroscopy and is compared to the wild-type protein. It is shown that residues 30 to 40 become more rigid than the corresponding wild-type segment. Moreover, in contrast to the wild type, which prefers to adopt two anti-parallel helices, the shuffled variant prefers to adopt a single helix.