Structural and functional modularity of voltage-gated potassium channels

Sequence similarity among known potassium channels indicates the voltage-ga ted potassium channels consist of two modules: the N-terminal portion of th e channel up to and including transmembrane segment S4, called in this pape r the 'sensor' module, and the C-terminal portion from transmembrane segmen t S5 onwards, called the 'pore' module. We investigated the functional role of these modules by constructing chimeric channels which combine the 'sens or' from one native voltage-gated channel, mKv1.1, with the 'pore' from ano ther, Shaker H4, and vice verse. Functional studies of the wild type and ch imeric channels show that these modules can operate outside their native co ntest, Each channel has a unique conductance-voltage relation. Channels inc orporating the mKv1.1 sensor module have similar rates of activation while channels having the Shaker pore module show similar rates of deactivation, This observation suggests the mKv1.1 sensor module limits activation and th e Shaker pore module determines deactivation, We propose a model that expla ins the observed equilibrium and kinetic properties of the chimeric constru cts in terms of the characteristics of the native modules and a novel type of intrasubunit cooperativity. The properties ascribed to the modules are t he same whether the modules function in their native contest or have been a ssembled into a chimera, (C) 1999 Federation of European Biochemical Societ ies.