Figure 11

High resolution structures of (A) rabbit Cav1.1 channel (PDB: 6jpa, 2.6 Å resolution, (Zhao20), (B) human Nav1.7 channel (PDB: 6j8g), 3.2 Å resolution (Shen21) and (C) human Cav3.1 channel (PDB: 6kzp , 3.1 Å resolution (Zhao et al.18). PDB files are illustrated using PyMOL Molecular Graphics System, Version 2.3, Schrödinger, LLC, https://pymol.org/2/. Left panels: side view of nanoparticle channel complex with voltage-sensor domains (magenta color) and pore loop domains (light pink color) with bound accessory subunits: Cavβ1, Cavα2δ1(light blue color): Navβ1, Nav β2 (light green color). Extracellular loop regions of ion channels bound to accessory subunits are highlighted darker blue (for Cav1.1) and highlighted darker green (for Nav1.7). Cysteine bonded pairs in the extracellular loops are labelled (mustard yellow color), with key negatively-charged (red color) and positively-charged (blue color) residues of the pore selectivity filter, indicated. Middle panels (side view) and right panel (top down view) of the opposing DI–DIII and DII–DIV pore loops alone (s5-P-s6), plus DI s1–s2 loop which contains a cysteine bonded to a cysteine in DII L5 (s5-P) loop in Cav3.1. The positioning of the unique cysteine-rich extracellular loops contained in non-vertebrate Cav3 channels in DII s5-P (between F891–D902) and DIV P-s6 (between D1791–Y1798) are labelled, by darker-purple dotted lines.