Potassium selectivity filter

Figure 12.11 Schematic diagram of the ion pore of the K+ channel. From the cytosolic side the pore begins as a water-filled channel that opens up into a water-filled cavity near the middle of the membrane. A narrow passage, the selectivity filter, links this cavity to the external solution. Three potassium ions (purple spheres) bind in the pore. The pore helices (red) are oriented such that their carboxyl end (with a negative dipole moment) is oriented towards the center of the cavity to provide a compensating dipole charge to the K ions. (Adapted from D.A. Doyle et al.. Science 280 69-77, 1998.)...

Figure 9.4 Structures of potassium channels in open and closed conformations. The selectivity filter is orange, and the conserved glycine residue is in red. (From Yu et al., 2005. Reproduced with permission of Blackwell Publishing Ltd.)...

Finally, it is worth keeping in mind that the protein may be perturbed reversibly by the conditions of the NMR experiment. For example, a recent study demonstrated that removal of the bulk buffer that typically separates from the sample during magic angle spinning reversibly altered the conformation of the selectivity filter of the KcsA potassium channel addition of buffer to the rotor restored the conformation.101 Based on this observation of a hydration-induced shift in conformation, it seems prudent to maintain high hydration levels for NMR studies of proteins in general. 

In all five simulations, no significant differences in overall RMSD were observed, suggesting that the presence or absence of potassium ions had no effect on the overall conformation of the protein. However, a distinct influence of potassium ions on the conformation of the part of the helix that acts as a selectivity filter was found. The simultaneous presence of two potassium ions stabilized the conformation observed in the X-ray structure. The potassium ions and water molecules within the pore showed a concerted movement of a water-K+-water-K+ column on a time scale of several hundred picoseconds. 

A number of different X-ray structures of bacterial potassium channels reveal the detailed atomic picture of the pore-forming part, helices S5 and S6 [9]. KcsA, which is crystallized in the closed conformation, has an overall structure similar to an inverted teepee [9a], Four identical subunits surround the ion-conducting pathway (Figure 8.2). Each subunit contains two full transmembrane helices, S5 and S6, as well as the P loop. The S6 helices line the central cavity, whereas the S5 helices are involved in interactions with the lipid environment. In the closed channel conformation the transmembrane helices meet at the cytosolic side to block the ion conduction path. In the open conformation of the channel, the S6 helix kinks at a conserved glycine residue to open the ion conduction path, as shown in the structure of the bacterial channel MthK [10], The ion conduction path is formed by the selectivity filter and the large water-filled central cavity. 

Chloride channels have a completely different structure from potassium channels [15]. The dimeric structure has two ion pathways, one formed by each monomer. The ion pathway does not run straight through the membrane, but is U-shaped. Amino acids stabilize the ion in the pathway by forming direct interactions with the chloride atom via hydrogen bond donors, just as the carbonyl groups in the selectivity filter of potassium channels stabilize the potassium cation. 

Potassium channels are 100-fold as permeable to K+ as to Na+. How is this high degree of selectivity achieved The narrow diameter (3 A) of the selectivity filter of the potassium channel enables the filter to reject ions having a radius larger than 1.5 A. However, a bare Na+ is small enough (Table 13.2) to pass through the pore. Indeed, the ionic radius of Na+ is substantially smaller than that of K+. How then is Na+ rejected ... 

Figure 13.24. Selectivity Filter of the Potassium Channel. Potassium ions interact with the carhonyl groups of the TVGYG sequence of the selectivity filter, located at the 3-A-diameter pore of the potassium channel. 

Figure 13.25. Energetic Basis of Ion Selectivity. The energy cost of dehydrating a potassium ion is compensated by favorable interactions with the selectivity filter. Because sodium is too small to interact favorably with the selectivity...

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