Fig. 5: The polyQ tract of TBP forms a helix stabilized by Gln side chain to main chain hydrogen bonds and an electrostatic interaction.

a Sequence, numbering and helical projection of peptide TBP-Q₁₆. The electrostatic interaction is color-coded in purple. b CD spectra of peptides TBP-Q₁₆ (black) and TBP-Q₂₅ (gold). c Scheme of the electrostatic interaction between Arg and Glu at physiological pH and its absence at acidic pH. d ¹³C-detected CACO spectra of the TBP polyQ tract at pH 7.4 (top, black) and 2.8 (bottom, dark red). e Residue-specific helicity of TBP at pH 7.4 (black) and 2.8 (dark red). Shades color-coded as in a are shown to guide the eye. f Region of the ¹H-¹⁵N HSQC spectra of TBP at pH 7.4 (left, black) and 2.8 (right, dark red) showing the N_ε2-H_ε21 correlations. g Strips from the 3D H(CC)(CO)NH spectra of TBP at pH 7.4 (left, black) and 2.8 (right, dark red) displaying the side chain aliphatic ¹H resonances of the first three Q residues in the polyQ tract. Strips were chosen from either N^H or N_ε2 for clarity. h Frames from the MD trajectory obtained for TBP. An orthogonal view of the helix is shown. In the left panel, a frame is shown where Arg13 (i) establishes an electrostatic interaction with E10 (i-3), represented by the purple dashed line. Simultaneously, both Gln11 and Gln12 establish bifurcated hydrogen bonds with Ile7 and Leu8, respectively (pink dashed lines). Right: a frame where Arg13 (i) establishes an electrostatic interaction with Glu9 (i-4), while the two bifurcated hydrogen bonds previously described are also present.