Fig. 5

Structural impact of variant effects. A–D KCNE1 structural model, coded by mean missense trafficking scores (A,B) or missense functional scores (C,D) at each residue on the same color scale as in Figs. 2F and 4F (Red = loss-of-trafficking/function, white = WT-like, blue = gain-of-trafficking/function). Dotted lines indicate the approximate location of the plasma membrane. (g) represents glycosylation sites. Panels B and D show KCNE1 in complex with KCNQ1 (green) and calmodulin (gray). E I _Ks complex showing locations of panels F and G. F Constrained KCNE1 residues (pink) that make contacts with KCNQ1. KCNE1 residue M62 forms a hydrophobic cluster with KCNQ1 residues F123, F127, and V241, whereas KCNE1 residues Y65 and S68 make polar contacts with KCNQ1 residues D242 and Q260, respectively. G Constrained KCNE1 residues (pink; F78, Y81, I82, W87) that make contacts with calmodulin. Residues on calmodulin not labeled. A PDB model and and Pymol session files with trafficking and functional scores overlaid on the structure are in Supplemental files 7–8