Structural basis of ligand activation in a cyclic nucleotide regulated potassium channel.
Here we describe the initial functional characterization of a cyclic nucleotide regulated ion channel from the bacterium Mesorhizobium loti and present two structures of its cyclic nucleotide binding domain, with and without cAMP. The domains are organized as dimers with the interface formed by the linker regions that connect the nucleotide binding pocket to the pore domain. Together, structural and functional data suggest the domains form two dimers on the cytoplasmic face of the channel. We propose a model for gating in which ligand binding alters the structural relationship within a dimer, directly affecting the position of the adjacent transmembrane helices.
Clayton
Gina M
GM
Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, CT 06520, USA.
Silverman
William R
WR
Heginbotham
Lise
L
Morais-Cabral
João H
JH
D000595:Amino Acid Sequence / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D000242:Cyclic AMP / Q000378:metabolism*; D019281:Dimerization; D015640:Ion Channel Gating / Q000502:physiology*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D012230:Rhizobiaceae / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D008024:Ligands; D015221:Potassium Channels; D000242:Cyclic AMP