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. 2020 Mar 13;6(11):eaax6999. doi: 10.1126/sciadv.aax6999

Fig. 1. DEER with modulation depth–based data analysis allows monitoring the conformational ensemble of Tau.

Fig. 1

(A) Tau domain organization (R1 to R4, pseudorepeats; N, two N-terminal inserts). Stars indicate labeling positions in singly spin-labeled Tau derivatives. Colored bars depict sequences spanned by labels in doubly spin-labeled Tau. (B) 3-Maleimido proxyl spin label side chains attached to cysteines. (C) Modulations with the dipolar modulation frequency ωdd characterize a DEER time trace calculated for a delta peak at 4 nm (green). Experimental intramolecular DEER time traces recorded for Tau-17*-291* are modulation free in the absence (black) and presence (orange) of Hsp90 indicating broad distributions of ωdd and thus a broad conformational ensemble. Effective modulation depths Δeff at t = 3 μs provide information about the Tau conformational ensemble without or with Hsp90. (D) A random coil (RC) model is in reasonable agreement with DEER results for several labeled stretches of Tau, e.g., Tau-17*-103*. (E) Experimental results, e.g., for Tau-17*-433* suggest a considerably larger vicinity of spin labels than the RC simulation predicts, consistent with a paper-clip solution ensemble of Tau.