A symmetry-driven search for electrostatic interaction partners in charybdotoxin and a voltage-gated K+ channel.

A structural model of charybdotoxin bound to a Shaker K+ channel has emerged from mechanistic and mutagenic analysis of toxin-channel interactions. We test this model by predicting through-space electrostatic interactions between specific pairs of channel-toxin residues. Dissociation constants of channel-toxin variants, determined by radiolabeled toxin binding to Shaker-transfected COS membrane fragments, were used to identify pairs of residues located closely enough to interact electrostatically. The results further refine the structural model of the bound complex and produce a more detailed view of the vestibule of the Shaker channel.