Figure 10.

Alignment of transmembrane helices and P-helices in 4x6TM channels illustrating location of extracellular-loop cysteines. The pore module includes transmembrane helices S5, S6 (dark gray), and pore helices P1 and P2 (tan) on either side of the selectivity filter (SF). Conserved cysteines (yellow) are present in the variable-size extracellular loops (light gray). Eight core cysteines are located at positions 1-1, 1-2, 1-6, 3-1, 3-2, 4-3, and 4-6. Additional cysteines are found in Domain II of most vertebrate Na_v1 channels and T-type channels. All T-type channels also have conserved cysteines in S5P loops of Domain I (1-4,1-5) and Domain IV (4-1,4-2), as well as in the extracellular loop between S1-S2 segments of Domain I. Two additional cysteines unique to invertebrate T-type channels are found in Domain IV extracellular loop PS6, C-terminal to the P2 helix (4-4, 4-5). The alignment is obtained using sequences of 21 human 4x6TM channels, five invertebrate representatives from the giant pond snail Lymnaea stagnalis [LNALCN, LCa_v1, LCa_v2, LCa_v3-12a (-12b), LNa_v1 and LNa_v2], three representatives from unicellular coanoflagellate, Salpingoeca rosetta (SroCa_v1, SroCa_v3, and SroNa_v2) and TtrNa_v2, and the single representative from unicellular (non-animal) eukaryote, Thecamonas trahens.