A simple algorithm locates beta-strands in the amyloid fibril core of alpha-synuclein, Abeta, and tau using the amino acid sequence alone.

Fibrillar inclusions are a characteristic feature of the neuropathology found in the a-synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Familial forms of a-synucleinopathies have also been linked with missense mutations or gene multiplications that result in higher protein expression levels. In order to form these fibrils, the protein, a-synuclein (a-syn), must undergo a process of self-assembly in which its native state is converted from a disordered conformer into a ß-sheet-dominated form. Here, we have developed a novel polypeptide property calculator to locate and quantify relative propensities for ß-strand structure in the sequence of a-syn. The output of the algorithm, in the form of a simple x-y plot, was found to correlate very well with the location of the ß-sheet core in a-syn fibrils. In particular, the plot features three peaks, the largest of which is completely absent for the nonfibrillogenic protein, ß-syn. We also report similar significant correlations for the Alzheimer's disease-related proteins, Aß and tau. A substantial region of a-syn is also of converting from its disordered conformation into a long amphipathic a-helical protein. We have developed the aforementioned algorithm to locate and quantify the a-helical hydrophobic moment in the amino acid sequence of a-syn. As before, the output of the algorithm, in the form of a simple x-y plot, was found to correlate very well with the location of a-helical structure in membrane bilayer-associated a-syn.