Neurotoxic Oligomer’s Structure Uncovered

Using small-angle X-ray scattering (SAXS), an international research team has determined the low-resolution structure of α-synuclein oligomer, an aggregated protein intermediate thought to be part of the fibril formation process that is a hallmark of Parkinson’s disease (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1013225108). Scientists have suggested that oligomers, rather than protein monomers or fibrils, are the toxic species involved in the neurodegenerative disorder. But questions about the role of oligomers in fibril formation remain. Because SAXS can be applied in situ to a multicomponent solution, the researchers, led by Daniel E. Otzen of Denmark’s University of Aarhus and Bente Vestergaard of the University of Copenhagen, were able to probe the oligomers during fibrillation. Through ab initio modeling of the data, they found that α-synuclein oligomers are each composed of 16 monomers on average and have a wreathlike shape with dimensions of 180 × 90 Å. This shape and size suggest that an oligomer’s toxicity lies in its ability to perforate cell membranes, the researchers say, and that the toxic species are an integral part of fibril formation, stacking like coins to build the bundled filaments./p>