Learning by building: constructing voltage gated ion channels from individual modular components

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Voltage dependent K+ channels (Kv) are modular proteins; they are composed of a channel pore, a voltage sensor dornain and a linker, which connects the latter two parts. ln spite of detailed structui:al information on these important proteins there are still rnany open questions on the mechanism by which the voltage sensor movement results in an opening of the pore. Here we propose a new approach for tackling the basic mechanism of etectromechanical coupling between pore and voltage sensor in Kv channels. lt is based on the successful constructlon of a synthetic Kv channel from unrelated elements, a voltage indepenclent miniature K+ channel pore and the voltage sensor of the phosphatase from the tunicate Ciona intestinalis. ln a learning-by-building procedure we will construct and characterize new synthetic channels by systematically varying lhe structural and/or functional character of the pore, the voltage sensor and the linker respectively. The native combination of these defined elements in synthetic channels will provide in combination with theoreticaly based coarsed grain calculations mechanistic information on i) the impact of the linker in electromechanical coupling ii) the importance of the sensor domain for rectification iii) the impact of the voltage sensor on gating mechanisms, which are inherent in the pore.