Fig. 3: Agonist but not inverse agonist reduces the conformational dynamics of enNTS₁.

a Difference in deuterium uptake plots of enNTS₁ in apo-state and bound to NT8-13 at the time points 0 s (blue); 6 s (yellow); 60 s (orange); 6000 s (red); sum of differences (grey). b Relative deuterium uptake plots of apo state (red) and NT8-13 bound (black) for regions that show significant differences in deuterium uptake including the extracellular regions of TM1, D⁵⁶VNTDIYSKV⁶⁵; TM2, P¹²²VDVYN¹²⁷; TM7, F³⁴⁴DFHYF³⁴⁹; and ECL2, F²⁰⁶TMGLQNL²¹³. Data shown as intensity-weighted mean values ± standard deviation (n = 4). c Heatmap generated from DynamX 3.0 at 100 min overlaid on the structure of NTS₁ (PDB: 4XEE) (blue, least exchange, to red, maximum exchange). Peptides not observed by MS are coloured grey. d Difference in deuterium uptake plots of enNTS₁ in the apo-state and bound to inverse agonist SR142948A at time points 0 s (blue); 6 s (yellow); 60 s (orange); 6000 s (red); sum of differences (grey). e Relative deuterium uptake plots of apo state (red) and SR142948A-bound (black) show SR142948A has less impact on deuterium uptake than NT8-13 in the extracellular region of TM1 and ECL2 of enNTS₁. Data shown as intensity-weighted mean values ± standard deviation (n = 3). f Heatmap generated from HDX data (blue, least exchange, to red, maximum exchange) in apo state and in the presence of SR142948A on the structure of NTS₁ (PDB: 4XEE). Source data for this figure are provided as a Source data file.