Figure 10.

Localization of deafness-causing mutations in TMC1. A, Ribbon representation of the TMC1 cavity built by TM domains TM4–TM7. The side chains of residues L410 (green), G411 (cyan), M412 (magenta), T416 (blue), D528 (red), W554 (yellow), and D569 (orange) are depicted in ball and stick representation. The approximated location of the lipid carbonyls of the plasma membrane is represented with two planes of gray spheres and the intracellular (IC) and extracellular (EC) sides are indicated. D and E dashed lines indicate the planes shown in panels D, E, respectively. B, Surface representation of the TMC1 ion conduction cavity embedded in a lipid membrane. Residues L410, G411, M412, T416, D528, W554, and D569 are colored as in A. Phospholipids are shown in ball and stick representation with their aliphatic chain in gray, phosphate in orange, oxygen in red, and nitrogen in blue. C, Pore profile along the cavity indicating the approximated positions of the EC and IC and residues M412, T416, D528, and D569. D, Surface representation of the top view of the TM4–TM7 cavity from the extracellular side revealing the localization of D528 (red) at its narrower region. E, Surface representation of the top view of the cavity from the extracellular side revealing the localization of D569 (orange), T416 (blue), and M412 (magenta) at the wider region of the cavity. The asterisks in D, E indicate the potential ion permeation pathway.