Crystal structure and mechanism of a calcium-gated potassium channel

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 Ca²⁺. We have cloned, expressed, analysed electrical properties, and determined the crystal structure of a K⁺ channel (MthK) from Methanobacterium thermoautotrophicum in the Ca²⁺-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 Ca²⁺ binding in a simple manner to perform mechanical work to open the pore.