STRUCTUAL STUDIES OF POTASSIUM CHANNEL INTRACELLULAR DOMAINS AND ASSOC SUBUNITS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Voltage-dependent potassium channels (Kv) control the flow of K+ through the cell membrane in response to changes in membrane potential. Kv channels are central to many fundamental biological processes, such as nerve conduction, muscle contraction, and hormone secretion. We study the molecular mechanism of channel modulation at the atomic level. KCNQ is member of the Kv channel family. It has a large C-terminus domain and mutations within this domain causes arrythmias and seizure. We have crystallized the C-terminus domain. The crystals are small and initial tests on home detectors show that it diffracts to ~15 angstrom. We are currently refining the crystallization conditions. Kvbeta is an intracellular protein attached to a Kv channel. We have obtained Kvbeta crytals in complex a channel domain, and with small molecules that regulate channel function. The crystals diffract to ~3A at home source. The high intensity beam at CHESS will enable us to screen crystals and obtain high resolution data set on small crystals. We will only need monochromatic beam for these experiments.