This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Gating is the major mode of regulation of potassium channels; stimuli alter the equilibrium between the open and closed states of the ion pore letting ions flow through the channel. The structures of the KcsA channel (closed state) and the MthK channel (open state) revealed the molecular characteristics of the two gating states but we still do not understand clearly how stimuli induce the conformational change. We are working on the structure determination of a potassium channel that is gated by cAMP. We have recently determined the structure of its regulatory domain in both the bound and unbound conformations; this structure has provide interesting and important insights to the conformational changes that occur at the level of the cyclic-nucleotide binding domain upon ligand binding and has led us to proposed a model for channel gating. We are now expressing and growing crystals of the full-length channel. This tetrameric membrane protein has 6 putative transmembrane segments (TMs) per subunit; the last 2 TMs form the ion conduction pathway first revealed by the structure of the KcsA potassium channel; at the C-terminus there is a ~150 residue cytoplasmic cyclic-nucleotide binding domain. Presently, we are at the crystal screening stage and have already determined conditions to obtain crystals that diffract to 8 . We need access to beamtime to continue screening crystals that are emerging from conditions in different detergents.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR012408-12
Application #
7726268
Study Section
Special Emphasis Panel (ZRG1-BCMB-R (40))
Project Start
2008-09-18
Project End
2009-06-30
Budget Start
2008-09-18
Budget End
2009-06-30
Support Year
12
Fiscal Year
2008
Total Cost
$3,654
Indirect Cost
Name
Brookhaven National Laboratory
Department
Type
DUNS #
027579460
City
Upton
State
NY
Country
United States
Zip Code
11973
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