General Pore Features Revealed by Bacterial Channels

The problems with obtaining material for ion channel structural studies can be overcome by turning to bacterial ion channels. These molecules can be more readily expressed and purified in large quantities than their eukaryotic counterparts. The atomic details of the inner workings of an ion channel were first seen in the X-ray crystallographic structures of the bacterial potassium channel, KcsA (Fig. 4a) [6-9]. The KcsA structure revealed many of the general features of ion channel pores that had been anticipated from careful biophysical studies coupled with structural reasoning (see Chapter 36). For instance, many channels seem to be made on a funnel-shaped plan with a large entryway that tapers to a narrow constriction that can serve as a selectivity filter that allows only particular types of ions to pass.

Potassium channels are remarkable for their ability to discriminate between potassium and sodium ions with very high precision, preferring potassium by a factor of «10,000:1 [1].

Figure 3 Electron microscopy reveals the general features of the nictotinic acetylcholine receptor seen from the extracellular space at 9-A resolution, left, and the voltage-gated sodium channel at 25 A, right. The panels for the sodium channel show successive rotations of a surface representation of the channel and start from the extracellular side (0, 0) through the intracellular side (180, 0). The pairs of numbers indicate the degrees of rotation around the x and y axes. (Adapted from Unwin, N., Nature, 373, 37-43, 1995; Sato, C. et al., Nature, 409, 1047-1051, 2001.)

Figure 3 Electron microscopy reveals the general features of the nictotinic acetylcholine receptor seen from the extracellular space at 9-A resolution, left, and the voltage-gated sodium channel at 25 A, right. The panels for the sodium channel show successive rotations of a surface representation of the channel and start from the extracellular side (0, 0) through the intracellular side (180, 0). The pairs of numbers indicate the degrees of rotation around the x and y axes. (Adapted from Unwin, N., Nature, 373, 37-43, 1995; Sato, C. et al., Nature, 409, 1047-1051, 2001.)

Figure 4 Structural elements of a potassium channel pore. (Left) Two subunits from the KcsA potassium channel are shown. The transmembrane segments are labeled M1 and M2. M2 subunits cross at the region marked "Bundle" and restrict access to the channel pore. The pore helix is indicated by "P" and the selectivity filter is shown in yellow. The red star marks the inner cavity of the channel. (Right) Close-up view of the intimate contacts between the KcsA selectivity filter oxygens (red) and potassium ions (green spheres). (Adapted from Jiang, Y. et al., Neuron, 29, 593-601, 2001; Zhou, Y. et al., Nature, 414, 43-48, 2001.)

Figure 4 Structural elements of a potassium channel pore. (Left) Two subunits from the KcsA potassium channel are shown. The transmembrane segments are labeled M1 and M2. M2 subunits cross at the region marked "Bundle" and restrict access to the channel pore. The pore helix is indicated by "P" and the selectivity filter is shown in yellow. The red star marks the inner cavity of the channel. (Right) Close-up view of the intimate contacts between the KcsA selectivity filter oxygens (red) and potassium ions (green spheres). (Adapted from Jiang, Y. et al., Neuron, 29, 593-601, 2001; Zhou, Y. et al., Nature, 414, 43-48, 2001.)

Both ions are monovalent cations. A sodium ion has a radius of 0.95 Â, while potassium has a radius of 1.33 Â. How does the larger potassium ion pass through the potassium channel selectivity filter while the smaller sodium ion does not? Chemistry. All ions have shells of closely associated water molecules in solution [1]. For an ion to enter the filter, it must shed its waters of hydration. The selectivity filter of potassium channels is arranged in a way that displays rings of carbonyl oxygen atoms from the protein backbone at the exact diameter of a potassium ion. Thus, the waters of hydration surrounding a potassium ion are exactly replaced by oxygen atoms from the protein, creating a perfect chemical and energetic match as the ion enters the selectivity filter (Fig. 4b) [7,9]. Although the smaller sodium ion can pass through the filter, it is much more energetically costly, as fewer of its lost water ligands can be replaced by the channel. Other selectivity filters may work in a similar way in which the protein makes intimate contact with the permeant ion.

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