STRUCTURE DETERMINATION OF KEF CHANNEL CYTOPLASMIC DOMAIN COMPLEX

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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. KTN/RCK domains regulate the transmembrane flux of a variety of K+ transport systems and ion channels. Much controversy surrounds the mechanism of regulation, with alternative models proposing either, a constitutive, conformationally-flexible octameric ring of domains, or stoichiometric rearrangements between tetrameric and dimeric states, modulating ion flux. We are determining the structure of the KTN domain from the Kef K+ channel system, in complex with its KefF ancillary subunit to resolve this issue. Of additional interest, KefF binds FMN while the KefC KTN domain binds NAD(H), and together they form an enzymatically active complex capable of catalyzing novel redox chemistry. Thus, this study will also improve our understanding of how transmembrane ion conductance and cellular biochemistry can be linked to create higher order phenomena such as memory.