Calmodulation of Auditory Potassium Channels

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DESCRIPTION (provided by applicant): Calmodulin proteins are vital for both the assembly and regulation of auditory KCNQ channels. Although there are many informative high resolution structures of calmodulin bound to peptide fragments derived from ion channels, the location of calmodulin on functioning channels and the calcium-induced structural changes responsible for physiological function have remained elusive for all ion channels. This proposal outlines an innovative new approach that detects KCNQ-bound calmodulin and its distance from the ion conduction pathway. Using these experimentally determined distance restraints and the many high resolution structures of potassium channels and calmodulin bound to peptides, we will generate quaternary structures of the differently calcified KCNQ4- and KCNQ1/KCNE1-calmodulin complexes. These quaternary structures combined with the proposed functional studies will provide unprecedented molecular insight into calcium-regulated potassium recycling in the ear.