Membrane channel structure

Roux, B., 8c Schulten, K. (2004). Computational studies of membrane channels. Structure, 12, 1343. 

Figure 8. Schematic model of an oligomeric membrane channel structure by botulinum or tetanus neurotoxin. The model shows a trimer of the neurotoxin with smaller cylinders representing light chain whereas larger lobe representing heavy chain.

Parker, M., Buckley, J., Postma, J., et al., 1994. Structure of the Aeromonas toxin proaerolysin in its water-soluble and membrane-channel states. Nature 367 292-295. 

Gamma aminobutyric acid (GABA) receptors are located on the postsynaptic membranes of inhibitory synapses of both vertebrates and insects and contain within their membrane-spanning structure a chloride ion channel. They are found in both vertebrate brains and invertebrate cerebral ganglia (sometimes referred to as brains) as well as in insect muscles. Particular attention has been given to one form of this receptor—the GABA-A receptor—as a target for novel insecticides (Eldefrawi and Eldefrawi 1990). It is found both in insect muscle and vertebrate brain. The remainder of this description will be restricted to this form. 

The number of different proteins in a membrane varies from less than a dozen in the sarcoplasmic reticulum to over 100 in the plasma membrane. Most membrane proteins can be separated from one another using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), a technique that has revolutionized their study. In the absence of SDS, few membrane proteins would remain soluble during electrophoresis. Proteins are the major functional molecules of membranes and consist of enzymes, pumps and channels, structural components, antigens (eg, for histocompatibility), and receptors for various molecules. Because every membrane possesses a different complement of proteins, there is no such thing as a typical membrane structure. The enzymatic properties of several different membranes are shown in Table 41-2. 

The most likely way for pardaxin molecules to insert across the membrane in an antiparallel manner is for them to form antiparallel aggregates on the membrane surface that then insert across the membrane. We developed a "raft"model (data not shown) that is similar to the channel model except that adjacent dimers are related to each other by a linear translation instead of a 60 rotation about a channel axis. All of the large hydrophobic side chains of the C-helices are on one side of the "raft" and all hydrophilic side chains are on the other side. We postulate that these "rafts" displace the lipid molecules on one side of the bilayer. When two or more "rafts" meet they can insert across the membrane to form a channel in a way that never exposes the hydrophilic side chains to the lipid alkyl chains. The conformational change from the "raft" to the channel structure primarily involves a pivoting motion about the "ridge" of side chains formed by Thr-17, Ala-21, Ala-25, and Ser-29. These small side chains present few steric barriers for the postulated conformational change. 

Asymmetric membranes have a tight, low-permeability, retentive zone that performs the desired separation and a more open, high-permeability zone that provides mechanical strength to the overall membrane. This structure is particularly critical to the economic viability of reverse-osmosis membranes. Asymmetric membranes operated in TFF mode must have the tight side facing the feed channel so that particles are retained on its surface and can be acted upon by the tangential flow. Asymmetric membranes operated in NFF mode can... 

Some microbes are able to decrease the permeability of their membranes to prevent toxic metals from entering. If the toxic metals are not able to physically enter the cell, they will not be able to affect vital metal-sensitive structures, such as proteins. One way to prevent heavy metals from entering is by decreasing the production of membrane channel proteins.18 It is also possible for the metal-binding sites in the membrane and periplasm to be saturated with nontoxic metals.37 A third possibility is the formation of an extracellular polysaccharide coat, which binds and prevents metals from reaching the surface of the cell.24,38... 

Concerning the nature and structure of such amyloid peptide or protein channels, oligomers with annular morphologies have in fact been observed by EM for a-synuclein (Lashuel et al., 2002) and equine lysozyme (Malisauskas et al., 2003) even in the absence of any lipids or membranes. Channel-like structures have also been reconstituted in liposomes and observed by SFM for A/ i 4o, A/ j 42, human amylin, a-synuclein, ABri, ADan, and serum amyloid A (Fig. 5A Lin et al., 2001 Quist et al., 2005). Doughnut-shaped structures with a diameter of 10-12 nm and a central hole size of 1-2 nm (Fig. 5B) were imaged on top of lipid membranes (Quist et al., 2005). However, the radius of curvature of the SFM tips meant that it is not possible to say whether the pores were really traversing the lipid bilayer. 

These observations suggest that the trans-azo ammonium can stabilize the supramolecular channel structure, which is formed by assembling relatively hydrophilic oligoether units based on the molecular recognition in the membrane phase. Compared to the extended molecular form of the trans-azo compound, which is appropriate for covering the hydrophilic component from the outside, the cis compound with a bulky structure cannot stabilize the structure and hence prohibits the assembly formation because it requites a large void structure in the membrane. Therefore, only leaky currents are observable (Figure 26). 

Figure 26. Scheme for the control of ionic fluxes by light irradiation. trans-Azo ammonium, covering the hydrophilic oligoether parts from the outside, can stabilize the supramolecular ion channel structure, while cis cannot because of its bent structure. Therefore, trans-azo generates ion channel currents, while for c/sonly small leak currents across the membrane. 

Control of Permeability through Intramolecular Channels. Control of membrane permeability is effected in a most sophisticated and efficient manner in ligand-gated ion channels having discrete molecular entities with well-defined channel structures. Cyclodextrin derivatives of type 41 and 53 are interesting... 

Left and center Two gramicidin A molecules associate to span a cell membrane. Right Axial view showing ion channel. [Structure from B. Roux, "Computational Studies of the Gramicidin Channel." Acc. Chem. Res. 2002,35,366. based on solid-state nuclear magnetic resonance. Schematic at left from L. Stryer. Biochemistry,... 

It is well known that inward K+-channels at the plasma membrane are organized as tetramers, with the assembly of the four identical subunits making up a single pore for the permeation of K+ [58]. By contrast many other cation channels are composed of single polypeptides in which a set of domains corresponding to the subunit of the inward K+-channels is repeated four times to form the channel structures [58, 59]. It is therefore reasonable to suppose that cAMP-sensitive ion channels for the permeation of ions other than K+ exist and function in plant plasma membranes. The activation of these unidentified channels in response to... 

Beginn developed Percec-type dendrimers, which are known to form supramolecu-lar channels, with polymerizable acrylate groups in order to obtain ion-permeable membranes [97-99]. First, the dendron 78 (Scheme 40) was dissolved in a polymerizable acrylate mixture that does not shrink on polymerization. The second step was the thermo-reversible gelation of the acrylate mixture, which was followed by the last step, polymerization to fix the supramolecular channel structure (Scheme 40). In the first experiments, compounds with only one polymerizable group were used but it turned out that the gelating properties were not sufficient [100, 101] so threefold modified 78 had to be developed. 

Just as there are cation channels, there are also trans-membrane channels involved in the transport of biologically important anions such as Cl-. The crystal structure of the CIC chloride channel from Salmonella typhimurium was reported in 2002.3 Along with the determination of the Streptomyces lividans potassium channel structure, this work won a share of the 2003 Nobel prize in chemistry for Roderick MacKinnon (Howard Hughes Medical Institute, New York, USA). Chloride channels catalyse the flow of chloride across cell membranes and play a significant role in functions such as... 

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