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. Author manuscript; available in PMC: 2019 Aug 22.
Published in final edited form as: Neuron. 2018 Aug 22;99(4):736–753.e6. doi: 10.1016/j.neuron.2018.07.033

Figure 8. TMC1 Homology Model with Proposed Permeation Pathway.

Figure 8.

Homology model for TMC1 transmembrane domains S3–S8 with cysteine substitutions mapped onto the structure. The model shows the human sequence with F1 helix positions after 100 ns molecular dynamics equilibration of side chains. This may represent an open conformation, as channel closure is unlikely during the simulation time.

(A) A single TMC1 monomer shown from within the cell membrane. The various cysteine substitutions are color coded as follows: green substitutions had no effect; gold residues altered calcium selectivity after MTSET application; and magenta residues altered both calcium selectivity and current amplitudes after MTSET application. Cysteine substitution of the one red residue (N447) eliminated current entirely, even without MTSET application.

(B) View of domains 3–8 from outside the cell.

(C) View from inside the cell.