Fig. 3.

Secondary chemical shifts analysis reveals that the distal N-termini of the human TRPV1, TRPV2 and TRPV3 channels are highly disordered. (i-vii) Secondary chemical shifts are calculated as the differences between the experimentally determined and predicted C^α, C^β, C´, N´, H^N, H^α, H^β chemical shifts. POTENCI (Nielsen and Mulder 2018) was used for sequence-based prediction of random coil chemical shifts. (viii) Secondary structure propensity (SSP) prediction based on chemical shifts using the SSP script (Marsh et al. 2006). A positive and negative SSP score reflects α-helix and β-sheet propensities, respectively. A SSP value of 1 reflects a fully formed helical-structure and a value of -1 a fully formed βstrand, respectively. Only ¹³C^α, ¹³C^β and ¹H^α chemical shifts of non-proline preceding residues were used when running the SSP script. For better comparison with Fig. 1, the regions with low predicted disorder propensities based on ODiNPred are shaded in light grey. The stretch of residues (P103-R113) in the C-terminal region of the hsTRPV3-IDR potentially forming an α-helical element is highlighted in light purple. Of note, ODiNPred does not predict secondary structure formation for this region in TRPV3 (Fig. 1 C)