Possible role of the interfacial gating triad in electromechanical coupling in KV channels. (A, left) A bottom-up view of the PDs of the KV1.2/2.1 paddle chimera with the nonadjacent pairs of subunits colored similarly. The residues constituting the coupling cuff (R394, E395, and Y485) are depicted in a stick representation (and colored in blue, red, and green, respectively). (right) An enlarged view of the interfacial triad at a single intersubunit interface with the residues shown in CPK representation. (B) Cartoon of the S4-S5 linker and S5 hinge region in the WT channel and in the Y485A mutant. In WT, the hinge between the S4–S5 linker (S4–S5L) and the S5 is flexible, whereas in the Y485A mutant, the hinge is rigid. In WT, the force is transmitted from the S4 to the S4–S5L (curved solid red arrow) and relayed efficiently to the tail end of the S6 (straight solid red arrow), whereas only a small fraction is transmitted to the S5 (dashed curved red arrow). In the Y485A mutant, most of the force transmitted to the S4–S5L (from the S4) is lost in transmission to the S5 (curved solid red arrow) and only a small fraction is transmitted to the S6 (dashed straight red arrow). Thus, by altering the hinge-flexing energetics at the distal hinge of the S4–S5L, the Y485A mutation facilitates electromechanical transduction.
