Fig. 5
MK-886 binds and perturbs tau monomer conformation. (A) Single-molecule FRET (smFRET) measurements in the absence and presence of MK-886 with WT 2N4R tau double labeled at the proline-rich region/microtubule binding region (PRR/MTBR, left) or at the N-terminal domain (right). Tau schematic represents the labeling position for each construct. The black line is drawn from the peak of the histogram in buffer for comparison with DMSO and MK-886 samples. Representative histograms are shown. (B) Quantification of the smFRET measurements indicates that the PRR/MTBR becomes substantially more compact (increase in FRET) on binding MK-886 (5 μM) (A, bottom left) when compared with tau in buffer (A, top left) or DMSO (A, middle left), whereas the N-terminal domain (C) shows only minor differences in the presence of MK-886 (5 μM) (A, right). (D) FRET analysis of the dose response of…
