Fig. 1. Structural features of the Ca²⁺-bound mTMEM16A channel.

A The overall dimer structure with key TM helices highlighted (PDB: 5oyb). B, C Front and top views of the putative conducting pore. The pore profile calculated using HOLE³⁹ is illustrated using the green dots. The two key hydrophobic residues, L547 and I641, in the “neck” region are shown in yellow sticks. The pore-lining TMs are colored in blue (3 and 4), red (5) and green (6), respectively. The other TMs are colored in yellow. The bound PIP₂ molecule is represented as sticks in panels B and C. D Cartoon representation of the functional domain organization of TMs from the top. The pore-forming domain consists of the PIP₂-binding regulatory module (TMs 3-5) and Ca²⁺-binding activation module (TMs 6–8). TMs 1, 2, 9, and 10 form the dimerization and supporting domain.