References:	Doyle, D. A., Morais Cabral, J., Pfuetzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. L., Chait, B. T., MacKinnon, R.: The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280 pp. 69 (1998) Fundamentals of Biochemistry,D. Voet, J.G Voet, and C.W. Pratt, J. Wiley & Sons, Inc., 1999. pp267-268 Neuroscience, D. Purves, G.J. Augustine, D. Fitzpatrick, L.C. Katz, A. LaMantia, J.O. McNamara, S.M. Williams, Sinauer Associates, Inc.,2001. pp.87-89.
Biological Importance:	The Potassium channel is a membrane protein. It is usually voltage gated and it is involved in electrical signaling. Potassium channels are involved in just about everything that we do. They are involved in the action potentials that send electrical signals through the body that control everything from movement to seeing and thinking.
Structure & Function	The potassium channel has sequence similarity to all known potassium channels, meaning that the channel is virtually identical in all species, especially in the pore region. The pore also resembles the general structure of Na+ and Ca++ channels as well. The channel takes the form of a tetramer with 4 identical chains/subunits that create an inverted teepee or cone that surrounds the central pore and cradles the most important part of the channel, the selectivity filter. Both extracellular and intracellular entryways are negatively charged by amino acids. It has 2 layers of aromatic amino acids (~34Å apart) positioned to extend into the lipid bilayer near the membrane-water interfaces . Each chain/subunit contains 2 transmembrane alpha helices connected by the pore region which consists of the turret, pore helix, and selectivity filter. The narrow selectivity filter is only 12 Å long, whereas the remainder of the pore is wider and has a relatively inert hydrophobic lining. These structural and chemical properties favor a high K+ throughput by minimizing the distance over which K+ interacts strongly with the channel. A large water-filled cavity and helix dipoles help to overcome the high electrostatic energy barrier facing a cation in the low dielectric membrane center. The K+ selectivity filter is lined by carbonyl oxygen atoms, which provide multiple closely spaced sites . These oxygens compensate for the water oxygen atoms lost by the K+ ion and act as a surrogate water. The structure reveals that the selectivity filter is held open as if to prevent it from accommodating a Na+ ion with its smaller radius. It is thought that the K+ ion fits in the filter precisely so that the energetic costs and gains are well balanced. The structure of the selectivity filter with its molecular springs holding it open prevents the carbonyl oxygen atoms from approaching close enough to compensate for the cost of dehydration of Na+ or other smaller ions, however larger ions such as Rb+ and Cs+ are in fact let through sometimes because their size is so close to that of K+ ion (K+ ions are 10000 times more permeable that Na+ ions). The repelling forces between the K+ ions along with the the other forces then help to push the ions rapidly through the channel at a rate close to the that of diffusion.

 
 

Active Site Amino Acids	Ligand	Function
VAL76  GLY77  TYR78  GLY79	K+	Interacts perfectly with dehydrated K+ ions and very few other ions, allowing for high selectivity and rapid movement of K+ ions.

Daniel Marks
Copyright © 2001
 

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