Fig. 4: Structure basis for blockade of Ca_V3.3 by otilonium bromids.

a Chemical structures of OB. b The cryo-EM density shown in blue mesh for OB in sticks. c Hydrophobic residues which surrounding the D_II-D_III fenestration site and penetrated by OB are shown in sticks and overlaid with transparent surfaces viewed in facing the D_II-D_III fenestration site. OB is shown as brown sticks. d Detailed binding sites of OB in the pore domain. The side chains of key residues are displayed in sticks and overlaid with transparent surfaces. Black dashed lines indicated potential hydrogen bonds. Phospholipids entering through other fenestrations are shown as gray sticks. e Binding site of OB in Ca_V3.3^OB with Ca_V1.1 (PDB ID: 5GJV) (neon green) structures. The domains of Ca_V3.3^OB are colored as D_I in purple, D_II in green, D_III in blue, and D_IV in salmon. Extracellular view sectioned below the selectivity filter indicates OB penetrates through the D_II-D_III fenestration site of Ca_V3.3^OB (left panel) and Ca_V1.1(middle panel). Comparison of key residues in the pore domain between Ca_V3.3^OB and Ca_V1.1 is shown in the right panel.