Fig. 1: Tau is a high-affinity substrate of the Hsp70/Hsp90 chaperone machinery.

a Cartoon representation of Tau interacting with the Hsp70/Hsp90 chaperone machinery. b Native PAGE analysis of the Hsp70:Hop:Hsp90 complex (1:1:1 molar ratio) with increasing concentrations of Tau. Hsp70 and Hsp90 are abbreviated as “70” and “90”, respectively. For Hsp70, a fraction of the protein was oligomeric (labeled as “70 olig”). c Quantitative analysis of the band intensities from (b). Data are presented as mean ± the standard deviation (SD) from three independent experiments. d Tau affinities for the Hsp70/Hsp90 chaperone machinery in the absence (red) and presence of AMP-PNP (rose), as well as for the individual chaperones Hsp70 and Hsp90 reported previously (2),(1)^40,64 and confirmed for the Hsp90:Tau interaction (gray). Errors represent SD from three independent experiments (70Hop90:Tau) or standard error of the nonlinear fit (70Hop90:Tau^AMP-PNP and 90:Tau). e 2D ¹⁵N-¹H HSQC spectra of Tau alone (gray) and with increasing concentrations of the Hsp70:Hop:Hsp90 complex (1:1:1 molar ratio) using Tau:machinery molar ratios of 1:0.2 (purple), 1:1 (pink) and 1:2 (red). f NMR interaction profile observed in (e) (same color code). I₀ are the peak intensities of unbound Tau (gray spectrum in (e)). The black dotted line marks the distinction between fast (to the left) and intermediate-to-slow exchange (to the right) referring to low and high affinity, respectively. Tau domains are indicated on top. Source data are provided as a source data file.