Extended Data Figure 8. Amlodipine binding breaks symmetry.

a, The overall structure of Ca_VAb in complex with amlodipine (shown in ribbon representation). Measuring the C_α distances of V196 (nearing the amlodipine binding pocket) from the 4 subunits shows the channel is asymmetrical. b, Binding of amlodipine (sticks in red) induces asymmetry and causes rearrangement of the lipid in the central cavity. c–f, The amlodipine binding pocket showing the C_α–C_α distance at two layers (Y195–G164 and I199–F167) horizontally. At layer 1 (Y195–G164), the C_α–C_α distance of its neighbouring sites (11.0 Å in d and 11.0 Å in f) matches the drug binding site (10.9 Å in c), but the diagonal site (e) is too narrow (10.6 Å). At layer 2 (I199–F167), the pocket width of the diagonal site (11.1 Å in e) matches the drug-binding site (11.0 Å in c), but the two diagonal sites are too wide (11.4 Å in d and 11.3 Å in f).