Abstract
The formation of fibrillar tangles of the Tau protein is crucial in the development of Alzheimers disease. Biophysical methods based on labelling of the cysteines of Tau with fluorescence dyes would allow to study fibril formation with an internal eye. However, the two native cysteines of Tau at positions 291 and 322 are located in the repeat domain, which is involved in forming the fibrils. The contribution of both cysteine to this process is unclear. Here we show that blocking natural cysteines using large fluorescent dyes does not interfere with Tau fibrillation so that FRET can be used to follow structural changes during the process. We anticipate that cysteine-labelled Tau enables following structural rearrangements during fibril formation in detail. This may also allow to monitor the effect of drugs, small molecules and proteins on the process.
