Figure 1: Cartoon of the full-length tau sequence, showing the major regions and location of the K18 sequence.
From: A mechanistic model of tau amyloid aggregation based on direct observation of oligomers
Tau is alternatively spliced in vivo, with two possible inserts near the N terminus (N1 and N2) and one in the carboxyl-terminal half (R2). Repeats 1–4 (R1—R4), each 31 or 32 residues, represent the core of the filaments. The amino-terminal half of tau is termed ‘projection domain’ because it does not bind to the microtubule wall. The point deletion ΔK280 (indicated in red) located in one of the two hexapeptide motifs responsible for aggregation of tau into filaments43, and the substitution P301L (indicated in purple) that occur in FTD strongly enhance the β-sheet-forming propensity. The anti-aggregant PP mutant contains two substituted proline residues at positions I277 and I308 (indicated in blue). The K18 construct11, consisting of the four repeat regions, has been adapted for this work through three mutations—C291A and C322A (black dots) and I260C (black star) to allow specific fluorophore Alexa labelling at position 260 using maleimide chemistry.
