Structural features of the TMEM16 family. (A) Ribbon representation of the nhTMEM16 structure. The view is form within the membrane. Bound Ca²⁺ ions are shown as blue spheres. (B) View on the subunit cavity. The relationship to A is indicated. The position of the residue equivalent to Lys588 of mTMEM16 is shown as a black sphere and labeled. Corresponding positions of amino acids that have been shown to change ion conduction in mTMEM16 (Yu et al., 2012) are shown as red spheres. (C) Surface representation of the subunit cavity. The view is as in B. The location of polar and charged residues is shown in cyan. (D) Structure of the Ca²⁺-binding site. The relation to B is indicated. Ca²⁺ ions are shown as blue spheres, and side chains of interacting residues are shown as sticks. The numbering of selected residues corresponds to mTMEM16A. (E) Schematic representation of TMEM16A containing two pores that are independently regulated by Ca²⁺. (F) Hypothetical alternative arrangement of subunits resulting in a single pore.