Fig. 1.

Characterization of two coexisting conformations adopted by the TDP-43 N-domain. (A) Domain organization of the 414-residue TDP-43 protein, which is composed of the N-domain determined in the present study, nuclear localization signal (L), two RNA recognition motifs (RRM1 and RRM2) hosting a nuclear export signal (E), and C-terminal glycine-rich domain. (B) Far-UV CD spectra at protein concentrations of 15 µM of the N-domain (1–102) in Milli-Q water at pH 4.0 (blue line) and in 1 mM phosphate buffer at pH 7.5 (blue dotted line); N-domain (1–80) in Milli-Q water at pH 4.0 (red line) and in 1 mM phosphate buffer at pH 7.5 (red dotted line); and N-domain (10–102) in Milli-Q water at pH 4.0 (green line) and in 1 mM phosphate buffer at pH 7.5 (green dotted line). (C) Superimposition of the 2D NMR ¹H-¹⁵N HSQC spectra of the N-domain (1–102) in Milli-Q water at pH 4.0 at a at protein concentration of 40 µM (blue) and 1 mM (red). Cyan arrows are used to indicate the peaks from the well-folded form whose relative intensities are much higher at 40 µM (blue) than those at 1 mM (red). Purple arrows and oval are used to indicate the peaks from the unfolded form whose relative intensities are much lower at 40 µM (blue) than those at 1 mM (red). (D) Residue specific (ΔCα–ΔCβ) chemical shifts of the N-domain (1–102) in the folded (blue) and unfolded (red) forms.