? ? MthK and many other ligand-gated potassium channels share a common domain referred to as the regulator of K+ conductance (RCK domain). In MthK, the RCK domain is believed to use the free energy calcium binding to perform mechanical work on the ion conduction pore thereby opening the channel. We propose to investigate the hypothesis that the free energy release of ligand binding to the RCK domain induces a rearrangement of structure which is additive and propagated sequentially through transitional structures to a hinge point within the inner helices of the pore, causing them to swing open. Specifically, we plan to answer the following questions: (1) What are the structures of the RCK domain in the free and in the liganded conformations of the channel? (2) What interfaces between RCK domains are stabilized in the free and liganded conformations? (3) How is the structural rearrangement induced by ligand binding propagated to the pore region? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30NS051095-02
Application #
7176243
Study Section
Special Emphasis Panel (ZNS1-SRB-M (24))
Program Officer
Stewart, Randall R
Project Start
2006-01-01
Project End
2008-12-31
Budget Start
2007-01-01
Budget End
2007-12-31
Support Year
2
Fiscal Year
2007
Total Cost
$28,142
Indirect Cost
Name
Northwestern University at Chicago
Department
Pathology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611