80 mammalian genes that encode potassium channel subunits. However potassium channels found in bacteria are amongst the most studied of ion channels, in terms of their molecular structure. Using X-ray crystallography, profound insights have been gained into how potassium ions pass through these channels and why (smaller) sodium ions do not. The 2003 Nobel Prize for Chemistry was awarded to Rod MacKinnon for his pioneering work in this area. Selectivity filter Potassium ion channels remove the hydration shell from the ion when it enters the selectivity filter. The selectivity filter is formed by a five residue sequence, TVGYG, termed the signature sequence, within each of the four subunits. This signature sequence is within a loop between the pore helix and TM2/6, historically termed the P-loop. This signature sequence is highly conserved, with the exception that a valine residue in prokaryotic potassium channels is often substituted with an isoleucine residue in eukaryotic channels. This sequence adopts a unique main chain structure, structurally analogous to a nest protein structural motif. The four sets of electronegative carbonyl oxygen atoms are aligned toward the center of the filter pore and form a square anti-prism similar to a water-solvating shell around each potassium binding site. The distance between the carbonyl oxygens and potassium ions in the binding sites of the selectivity filter is the same as between water oxygens in the first hydration shell and a potassium ion in water solution, providing an energetically-favorable route for de-solvation of the ions. Sodium ions, however, are too small to fill the space between the carbonyl oxygen atoms. Thus, it is energetically favorable for sodium ions to remain bound with water molecules in the extracellular space, rather than to pass through the potassium-selective ion pore. This width appears to be maintained by hydrogen bonding and van der Waals forces within a sheet of aromatic amino acid residues surrounding the selectivity filter. The selectivity filter opens towards the extracellular solution, exposing four carbonyl oxygens in a glycine residue (Gly79 in KcsA). The next residue toward the extracellular side of the protein is the negatively charged Asp80 (KcsA). This residue together with the five filter residues form the pore that connects the water-filled cavity in the center of the protein with the extracellular solution. Selectivity mechanism The mechanism of potassium channel selectivity remains under continued debate. The carbonyl oxygens are strongly electro-negative and cation-attractive. The filter can accommodate potassium ions