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.