A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel

Voltage-gated K+ channels contain a central pore domain and four surroundin g voltage-sensing domains. How and where changes in the structure of the vo ltage-sensing domains couple to the pore domain so as to gate ion conductio n is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a star ting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore doma in in the Shaker voltage-gated K+ channel to localize potential protein-pro tein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the inter face between pore domain subunits. In contrast, mutants producing large cha nges in gating tend to cluster near this interface. These results imply tha t voltage-sensing domains interact with localized regions near the interfac e between adjacent pore domain subunits.