Ion symporters are membrane proteins that mediate the co-transport of two different ion species across themembrane. They play important roles in human physiology; the Na+/i- symporter, for example, is responsible for accumulation of I- in the thyroid gland. Despite their importance a detailed mechanistic understanding of how symporters work is lacking. The long term objective of this proposal is the development of a detailed molecular model for the co-transport oftwo ions, Na+ and K+ by KtrAB, a bacterial symporter. The major aims of this proposal are: 1 - Characterize the transport properties of the KtrAB symporter. 2 - Characterize the structure and function of KtrA. 3 - Determine the crystal structure of the membrane protein KtrB.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM068585-05
Application #
7265328
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Chin, Jean
Project Start
2003-08-01
Project End
2008-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
5
Fiscal Year
2007
Total Cost
$262,888
Indirect Cost
Name
Yale University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Clayton, Gina M; Aller, Steve G; Wang, Jimin et al. (2009) Combining electron crystallography and X-ray crystallography to study the MlotiK1 cyclic nucleotide-regulated potassium channel. J Struct Biol 167:220-6
Altieri, Stephen L; Clayton, Gina M; Silverman, William R et al. (2008) Structural and energetic analysis of activation by a cyclic nucleotide binding domain. J Mol Biol 381:655-69
Clayton, Gina M; Altieri, Steve; Heginbotham, Lise et al. (2008) Structure of the transmembrane regions of a bacterial cyclic nucleotide-regulated channel. Proc Natl Acad Sci U S A 105:1511-5
Albright, Ronald A; Joh, Kyu; Morais-Cabral, Joao H (2007) Probing the structure of the dimeric KtrB membrane protein. J Biol Chem 282:35046-55
Albright, Ronald A; Ibar, Jose-Luis Vazquez; Kim, Chae Un et al. (2006) The RCK domain of the KtrAB K+ transporter: multiple conformations of an octameric ring. Cell 126:1147-59