FIGURE 3. Low-pH-induced destabilization of the channel and opening of the Trp 41 gate.

a, ¹H-¹⁵N TROSY spectra of reconstituted M2(18–60) tetramer at pH 6.0, 6.5, 7.0 and 7.5, in the absence of rimantadine (-Rim.), recorded at 500 MHz ¹H frequency and 30 °C. Green, transmembrane helix; pink, amphipathic helix; black, N-terminal loop. b, The ¹⁵N R₂ (pure R₂ + R_ex) of the Trp 41 N1 as a function of the frequency of refocusing (1/_cp) of chemical shift evolution obtained at pH 7.5, 7.0 and 6.0, showing faster timescale motion of the Trp 41 gate as the channel is activated. c, Comparison between R₂(_cp) at pH 7.0 in the absence (blue) and presence (black) of rimantadine, demonstrating that the drug slows down the gate flipping at this pH.