Figure 1.

Nav1.7/N1245S and Nav1.7/E1139K variants are both located in intracellular loops of the Nav1.7 protein. (a) The N1245S variant is found in the intracellular linker between DIII S2 and S3 and E1139K is located in the large intracellular linker between DII and DIII. (b) Visualization of the hNav1.7 WT (left, light blue) and the N1245S variant (right, orange) protein structure associated with the β1 subunit (magenta) using PyMol. DI, DII and DIV are depicted in gray and DIII-DIV linker in salmon. DIII S0 to S6 segments are labeled in a range of blue colors. The S2-S3 linker (LS2-S3) of DIII is indicated in light salmon. (c) A magnified overlap view of (B) is shown with the variant N1245S in orange and the WT N1245 in light blue. DIII segments are labeled in black. (d) A detailed, slightly anti-clockwise turned view of the overlap in (C) reveals non-covalent bonds between N1245 (WT, left) or N1245S (variant, right) and two possible interaction partners. DIII segments are labeled in black