(a–b) Cutaway views of the neck region for the closed (a) and open (b) conformations, viewed from the extracellular side and shown as ribbons. Residues that form the hydrophobic seal in the closed conformation (I76, F80, F84) are colored red in both conformations. Surrounding aromatic residues that move to accommodate opening are colored green. Residues that become exposed to the pore in the open conformation (S79, sticks, and G83, sphere) are blue. Cyan spheres represent Ca2+ ions. A supplementary video shows the transition. (c–d) Side view of the conformational changes in the neck; closed (c) and open (d). In (c), a superposition of the structures of BEST1405 in the Ca2+-bound inactivated conformation, BEST1345 in the Ca2+-bound closed conformation, and BEST1345 in the Ca2+-free closed conformation shows that the neck adopts an indistinguishable (closed) conformation in each. The S2a,b, and c helices from three subunits are shown. Residues are depicted and colored as in a-b; P77 is gray; S87 is shown for reference. (e) A close-up view showing the hydrophobic packing of I76 in the open conformation. Neck residues are highlighted in red, neighboring hydrophobic residues that interact with I76 are shown in green, and P77 is depicted in gray. (f) Location of missense mutations associated with retinal diseases (Johnson et al., 2017; Xiao et al., 2010) at amino acid positions near the neck (red spheres indicate the Cα positions of the mutations).