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. Ion symporters are integral membrane proteins that co-transport two different ion species across the membrane. They play important roles in human physiology: the Sodium/Iodide symporter, for example, is responsible for accumulation of iodide in the thyroid gland. However, an atomic level mechanistic understanding of how symporters work is lacking. The long term goal of the first project is to obtain high resolution structures of an E. coli Sodium/Potassium symporter, TrkH, in complex with a regulatory intracellular protein, TrkA. We will address the questions of how the ion selectivity is achieved, and how the function of ion transport is regulated by intracellular ATP level.Voltage-dependent potassium channels (Kv) control the flow of K+ through the cell membrane in response to changes in membrane potential. The long-term goal of the second project is to develop an atomic level understanding of channel modulation mechanisms. In this project, we focus on modulation of Kv channel by beta subunit. We will solve high resolution structures of the beta subunit in complex with intracellular channel domains, in reduced and in oxidized forms. We will also solve structure of the beta subunit in complex with small molecule modulators that affect channel functions.