This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR012408-15
Application #
8363371
Study Section
Special Emphasis Panel (ZRG1-BCMB-R (40))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
15
Fiscal Year
2011
Total Cost
$10,338
Indirect Cost
Name
Brookhaven National Laboratory
Department
Type
DUNS #
027579460
City
Upton
State
NY
Country
United States
Zip Code
11973
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