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      Crystal structure and mechanism of a calcium-gated potassium channel.

      Nature
      Amino Acid Sequence, Bacterial Proteins, chemistry, genetics, metabolism, Calcium, pharmacology, Crystallography, X-Ray, Electrophysiology, Ion Channel Gating, drug effects, Ligands, Lipid Bilayers, Methanobacterium, Models, Molecular, Molecular Sequence Data, Potassium Channels, Calcium-Activated, Protein Structure, Quaternary, Protein Structure, Tertiary, Sequence Alignment, Structure-Activity Relationship, Thermodynamics

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          Abstract

          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.

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