A potassium ion channel from the bacterium Streptomyces lividans. It is a tetramer of four identical subunits, each of which contains two transmembrane alpha helices with a short pore helix region between them. The subunits assemble to form a shape resembling an inverted cone, with the apex facing the intracellular side of the plasma membrane. The selectivity filter is cradled in the base of the cone which faces the extracellular side.

Notable properties of potassium channels such as KcsA are their extremely high throughput - which approaches that of diffusion - and their high selectivity - potassium ions are roughly 10,000 times more permeant than the smaller but otherwise similar sodium ions. These properties would be expected to be mutually exclusive as high selectivity suggests a strong energetic interaction between the ions and the channel, which precludes high throughput.

The high selectivity is accounted for by the highly conserved selectivity filter (the potassium ion channel signature sequence), a region of five amino acids between the outer (N-terminal) transmembrane helix and the pore helix of sequence TVGYG. The carbonyl backbone of these residues faces into the pore, forming rings of negatively charged oxygen atoms of a fixed diameter. These interact with the potassium ions entering the channel in much the same way as a solvation shell of water molecules does. Sodium ions, with a smaller radius, are not as well "solvated" by this ring of negative charge as the position of the oxygen atoms is fixed. This makes the movement of potassium ions out of solution (dehydration) and through the channel more thermodynamically favourable than the dehydration of other ions of different sizes. The selectivity filter region of the pore can accomodate two potassium ions, and it is believed that the repulsion between these ions counters the attraction between the ion and the channel, increasing the rate at which ions move through the channel.

Once through the filter, the ions enter a large aqueous cavity lined with hydrophobic residues. Here, they are solvated by water molecules, which stabilizes them inside the lipid bilayer - a region of low dielectric which would be an energy maxima for the movement of the ion across the membrane. The helix dipoles of the carboxyl end of the pore helix also help to stabilize the ion's positive charge. As interaction between the ion and the channel is minimised - with the exception of the selectivity filter - a large throughput is achieved.

(See Doyle et al, Science, Vol 280 pp69, 3rd April 1998 and Schrempf et al, EMBO Journal, Vol 14 No 21 pp5170, 1995)

So why is KcsA important? Firstly, it has a great deal of homology in its pore region to virtually every other potassium-selective ion channel known, including the more complex voltage gated ion channels such as Shaker in Drosophila. Secondly, it is readily overexpressed in bacteria, whereas eukaryotic potassium channels are difficult to produce in this manner. Thirdly, it is one of the few integral membrane proteins to be successfully crystallized, alowing its structure to be analysed to about 3.2 angstroms with X-Ray crystallography, which is quite respectable for membrane proteins. This makes it invaluable as a model for more complex potassium channels.

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