Bacterial ion channels

Like the photosynthetic reaction center and bacteriorhodopsin, the bacterial ion channel also has tilted transmembrane helices, two in each of the subunits of the homotetrameric molecule that has fourfold symmetry. These transmembrane helices line the central and inner parts of the channel but do not contribute to the remarkable 10,000-fold selectivity for K+ ions over Na+ ions. This crucial property of the channel is achieved through the narrow selectivity filter that is formed by loop regions from thefour subunits and lined by main-chain carbonyl oxygen atoms, to which dehydrated K ions bind. 

All K channels are tetrameric molecules. There are two closely related varieties of subunits for K channels, those containing two membrane-spanning helices and those containing six. However, residues that build up the ion channel. Including the pore helix and the inner helix, show a strong sequence similarity among all K+ channels. Consequently, the structural features and the mechanism for ion selectivity and conductance described for the bacterial K+ channel in all probability also apply for K+ channels in plant and animal cells. 

Hagiwara T, Kijima-Suda I, Ido T, Ohrui H, Tomita K (1994) Inhibition of bacterial and viral sialidases by 3-fluoro-V-acetyIneuraminic acid, Carbohydr Res 263 167-172 Haskell TH, Peterson FE, Watson D, Plessas NR, Culbertson T (1970) Neuraminidase inhibition and viral chemotherapy, J Med Chem 13 697-704 Hatakeyama S, Sugaya N, Ito M, Yamazaki M, Ichikawa M, Kimura K, Kiso M, Shimizu H, Kawakami C, Koike K, Mitamura K, Kawaoka Y (2007) Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors, JAMA 297 1435-1442 Hay AJ (1992) The action of adamantanamines against influenza A viruses inhibition of the M2 ion channel protein, Semin Virol 3 21-30... 

Bacterial botulinum toxin blocks presynaptic acetylcholine release 725 Snake, scorpion, spider, fish and snail peptide venoms act on multiple molecular targets at the neuromuscular junction 727 Electrolyte imbalances alter the voltage sensitivity of muscle ion channels 728... 

Eukaryotic ABC transport system Phosphotransferase system (PTS) Ion-coupled transport system Signal Transduction Two-component system Bacterial chemotaxis MAPK signaling pathway Second messenger signaling pathway Ligand-Receptor Interaction G-protein-coupled receptors Ion-channel-linked receptors Cytokine receptors Molecular Assembly Ribosome assembly Flagellar assembly Enzyme assembly... 

The first synthetic antibiotics were the sulfonamides (right). As analogues of p-ami-nobenzoic acid, these affect the synthesis of folic acid, an essential precursor of the coenzyme THF (see p. 108). Transport antibiotics (top center) have the properties of ion channels (see p. 222). When they are deposited in the plasma membrane, it leads to a loss of ions that damages the bacterial cells. 

The existence of voltage-gated ion channels in bilayers are not limited to nerve membranes. They are present to some extent in all cell membranes. Even the paramecium has at least seven kinds of Na+, K+, and Ca2+ channels.483 Channels may also be formed by many peptide antibiotics. Among them are the human defensins (Chapter 31) and the 20-residue alamethi-cin. Six to eleven of the mostly helical monomers of that antibiotic assemble to form a single voltage-dependent channel.4844843 The bacterial toxin colicin El (Box 8-D) forms voltage-dependent channels within bacterial membranes.485... 

The simulation of ion channels and other pore-forming peptides and proteins at atomic detail is nowadays also possible. With the increase in computational power, these complex systems have attracted much more interest, and several simulations have been reported. Very often, only the transmembrane segments of the channel-forming proteins are included in the simulation to reduce the size and complexity of the system. The simulated systems range from synthetic model ion channels to a bacterial porine protein. 

The recent discoveries of PHB and polyP in a human calcium pump and bacterial potassium channel suggest that the naked PHB/polyP complexes found in bacteria are progenitors of protein ion transporters. The process by which protein channels and pumps may have evolved from PHB/polyP complexes is unknown however, one may surmise that over time proteins surrounded the complexes to support and regulate their activity. At first, the association may have been nonco-valent, but subsequently PHB may have become tethered to the protein by a covalent bond. By this view, many of the channels and pumps of prokaryotes and eukaryotes may be supramolecular structures in which protein, polyP, and PHB join together for efficient regulation of transmembrane ion transport. 

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. 

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