Ca-activated K+ channel
Methanothermobacter thermautotrophicus (archaea)
Ion channels play a central role in biological processes, signal transduction, cell volume regulation and movement. Ion channel proteins widely exist in the cell membranes, forming a conduction pathway, such as a pore, through which ions diffuse across the membranes. They control the conduction of ions by opening or closing a gate in the pore in response to an appropriate stimulus. In order to gain a better understanding of the mechanism of ion conduction, we need to know how ions selectively flow through the channel pores and how the channels open and close the gate in response to any stimuli. K+ channels are members of the family of tetrameric cation channels, which contain four membrane-spanning subunits or domains that form the central pore. It has been revealed that the cation selectivity for each channel is determined by the conformation of the pore, such as a special arrangement of cation-attracting pore alpha-helices.
The open-state structure of a K+ channel that opens and closes the gate of the pore in response to intercellular Ca2+ levels has been determined. This protein contains eight domains to regulate K+ conductance (RCK domains), which together form the gating ring on the surface of an intracellular membrane. Two RCK domains consist of a homodimer, as a rigid unit, producing a cleft between two domains to which Ca2+ binds. The gating ring opens and closes by using the free energy of Ca2+-binding. Based on this structural analysis, the mechanism of gate-opening and closing induced by ligand-binding has been proposed. When Ca2+ binds to the cleft of the gating ring, the shape of the cleft changes, inducing some tilt in each rigid unit. This results in pulling the inner helices of the pore, and opening the gate of the pore. Then when the Ca2+ ion is released, each rigid unit rotates causing a conformational change of the gating ring. This closes the gate of the pore.
Protein Data Bank (PDB)
JIANG, Y. LEE, A. CHEN, J. CADENE, M. CHAIT, B.T. MACKINNON, R.; "CRYSTAL STRUCTURE AND MECHANISM OF A CALCIUM-GATED POTASSIUM CHANNEL"; Nature; (2002) 417:515-522 PubMed:12037559.
author: Yuko Tsuchiya