Fig. 1: Characterization of pore residues by systematic mutagenesis.

a Cα representation of the pore contained in a single subunit of TMEM16A (PDB: 5OYB) with different regions indicated. Blue surface encloses the water-accessible volume of the pore calculated in HOLE⁵³ with a probe radius of 1.15 Å. b–e Summary of Ca²⁺ concentration-response relationships of Ala mutants in different regions of the pore. b Outer vestibule, c neck, d inner vestibule, and e Ca²⁺ binding site. Red indicates a left-shift, and blue a right-shift in the EC₅₀. Left, sections of the pore with Cα atoms of selected mutated residues shown as spheres and colored according to the effect on Ca²⁺ potency. Center, Ca²⁺ potencies of mutants. The logarithm of the fold-change in EC₅₀ of each investigated residue compared to wild type (WT) is shown. Individual measurements are displayed as circles, bars show averages of the indicated number of patches shown in Supplementary Tables 1–3, and errors are SEM. Right, histogram of EC₅₀ shifts in the corresponding region. a, e Ca²⁺-binding residues are shown as sticks and bound Ca²⁺ ions as green spheres.