Fig. 5. Anion binding pocket of pendrin, prestin, and SLC26A9 and disease-associated variants of pendrin.

a–c Details of inward-open anion binding pocket of pendrin, prestin, and SLC26A9. The important residues are shown. d–f Comparation of anion binding pocket positions among outward-open pendrin, intermediate prestin, intermediate SLC26A9, and outward-open AE1. g Fluorescence intensity change in HEK293T cells in Cl⁻/I⁻ exchange assay. n = 5 cells examined over 3 independent experiments. Blank, EYFP-transfected cells. Data are presented as mean values, error bars indicate SD. h Fluorescence intensity change in HEK293T cells in Cl⁻/HCO₃⁻ exchange assay. n = 5 cells examined over 3 independent experiments. Blank, non-transfected cells. Data are presented as mean values, error bars indicate SD. i Location summary of 761 disease-associated mutations in the resolved 655 amino acids of our pendrin model. Disease-associated mutations are cited from the deafness variation database (https://deafnessvariationdatabase.org; accessed on the 20 Sep 2022). NTD_di indicates the residue in the dimerization interface of NTD, EL indicates the extracellular loop, CL indicates the cytosolic loop, and STAS_di indicates the residue in the dimerization interface of STAS.