Crystal structure and mechanism of a calcium-gated potassium channel.
Ion channels exhibit two essential biophysical properties; that is, selective ion conduction, and the ability to gate-open in response to an appropriate stimulus. Two general categories of ion channel gating are defined by the initiating stimulus: ligand binding (neurotransmitter- or second-messenger-gated channels) or membrane voltage (voltage-gated channels). Here we present the structural basis of ligand gating in a K(+) channel that opens in response to intracellular Ca(2+). We have cloned, expressed, analysed electrical properties, and determined the crystal structure of a K(+) channel (MthK) from Methanobacterium thermoautotrophicum in the Ca(2+)-bound, opened state. Eight RCK domains (regulators of K(+) conductance) form a gating ring at the intracellular membrane surface. The gating ring uses the free energy of Ca(2+) binding in a simple manner to perform mechanical work to open the pore.
Jiang
Youxing
Y
Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Lee
Alice
A
Chen
Jiayun
J
Cadene
Martine
M
Chait
Brian T
BT
MacKinnon
Roderick
R
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects; D008024:Ligands; D008051:Lipid Bilayers / Q000378:metabolism; D017014:Methanobacterium / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D001426:Bacterial Proteins; D008024:Ligands; D008051:Lipid Bilayers; D024681:Potassium Channels, Calcium-Activated; D002118:Calcium