Monomeric channel

Cook, G. A. Prakash, O. Zhang, K. Shank, L. P. Takeguchi, W. A. Robbins, A. Gong, Y. Iwamoto, T. Schultz, B.D. Tomich, J.M. (2004) Activity and structural comparisons of solution associating and monomeric channel-forming peptides derived from the glycine receptor M2 segment Biophys. J. 86,... 

Each tetramer comprises four closely associated monomeric channels circled by a hydrophobic surface long enough to span the lipid bilayer (Fig. 4). Toward the cytoplasmic and periplasmic surfaces are layers that include side chains of tyrosine and tryptophan that can productively interact with the polar-nonpolar interface in the lipid head-group region as in other integral membrane proteins (Koeppe and Anderson, 1996). These layers are flanked by two outer layers of charged residues, 35 A apart, that result in net positive charge on the cytoplasmic side. 

All of the transport systems examined thus far are relatively large proteins. Several small molecule toxins produced by microorganisms facilitate ion transport across membranes. Due to their relative simplicity, these molecules, the lonophore antibiotics, represent paradigms of the mobile carrier and pore or charmel models for membrane transport. Mobile carriers are molecules that form complexes with particular ions and diffuse freely across a lipid membrane (Figure 10.38). Pores or channels, on the other hand, adopt a fixed orientation in a membrane, creating a hole that permits the transmembrane movement of ions. These pores or channels may be formed from monomeric or (more often) multimeric structures in the membrane. 

Paul At one stage it was postulated that the pentameric PLB formed a leak channel. There is a fair amount of evidence against this. Perhaps most striking is work by the Kranias laboratory in which the transgene for a PLB mutant which remains monomeric and does not form the pentamers was expressed in the heart. 

The monomeric PLB mutant was as potent (actually even more so) than the native PLB, which indicated that a PLB pentamer forming a leak channel was unlikely. There is a reported backflux through the Ca-ATPase which is lower in the PLB knockout. In the heart you can make a really good SR vesicle preparation for direct evaluation of SR Ca2+ uptake, but one of the limitations here is that this is difficult for smooth muscle tissues, though the bladder is useful for some quantitative biochemistry. So the question of a PLB leak is still open for smooth muscle but, on the basis of cardiac data, it is unlikely. 

The FhuA receptor of E. coli transports the hydroxamate-type siderophore ferrichrome (see Figure 9), the structural similar antibiotic albomycin and the antibiotic rifamycin CGP 4832. Likewise, FepA is the receptor for the catechol-type siderophore enterobactin. As monomeric proteins, both receptors consist of a hollow, elliptical-shaped, channel-like 22-stranded, antiparallel (3-barrel, which is formed by the large C-terminal domain. A number of strands extend far beyond the lipid bilayer into the extracellular space. The strands are connected sequentially using short turns on the periplasmic side, and long loops on the extracellular side of the barrel. 

A premixture of 8 and soybean lecithin gave stable single channel currents with well-defined transitions between open and closed states with the 0.1-Is time scale. The conductance level detected was 6.1 0.5 pS at 0.5 M KCl solution. At various transmembrane voltages with different molar ratios of 8-to-lipid in the range 1/200 - 1/3000, an identical conductance level was always observed. This observation is therefore compatible with the original idea that monomeric 8 itself defines a pore mouth with a specified diameter in the single lipid layer. It gave a cation/anion... 

Fig. 5.2. Structural principles of transmembrane receptors, a) Representation of the most important functional domains of transmembrane receptors, b) Examples of subunit structures. Transmembrane receptors can exist in a monomeric form (1), dimeric form (2) and as higher oligomers (3,4). Further subunits may associate at the extracellular and cytosohc domains, via disulfide bridges (3) or via non-covalent interactions (4). c) Examples of structures of the transmembrane domains of receptors. The transmembrane domain may be composed of an a-hehx (1) or several a-helices linked by loops at the cytosolic and extracellular side (2). The 7-helix transmembrane receptors are a frequently occurring receptor type (see 5.3). Several subunits of a transmembrane protein may associate into an ohgomeric structure (3), as is the case for voltage-controUed ion channels (e.g., K channel) or for receptors with intrinsic ion channel function (see Chapter 17).

Dividing the total reaction channels into monomeric and cross-molecular reactions, it is found that about 73% of the reaction channels involve cross-molecular reactions, compared to only 27% of monomeric reactions. The conclusion that follows from these numbers is that the molecular aggregate has a large effect on the photochemistry of pentanal and that it yields a much larger number of different products. It is predicted that longer simulation timescales or larger clusters will even more increase the cross-molecular reactions. Experimental evidences provided in the same Ref. [32] support most of the predicted reaction channels. 

FIGURE 11-46 Structure of an aquaporin, AQP-1. The protein is a tetramer of identical monomeric units, each of which forms a transmembrane pore (derived from PBD ID 1J4N). (a) Surface model viewed perpendicular to the plane of the membrane. The protein contains four pores, one in each subunit. (The opening at the junction of the subunits is not a pore.) (b) An AQP-1 tetramer, viewed in the plane of the membrane. The helices of each subunit cluster around a central transmembrane pore. In each monomer, two short helical loops, one between helices 2 and 3 and the other between 5 and 6, contain the Asn-Pro-Ala (NPA) sequences found in all aquaporins, and form part of the water channel, (c) Surface representation of a single subunit, viewed in the plane of the membrane. The near side of the AQP-1... 

One explanation is that the radiative transition probabilities of the excimers are similar to those of the monomeric singlet states, but the excimers are formed in much lower yields. This could be the case if the initially excited state (the optically bright state populated by absorption) forms the excimer state in competition with other decay channels. An alternative explanation is that the excimer states are formed in high yield, but have low radiative transition probabilities (i.e. they are relatively dark in emission). 

Meyer and coworkers investigated the photophysical behavior of vinyl containing Ru(II) and Os(II) complexes electropolymerized into the channels of silica sol-gel modified ITO electrodes. The monomeric complexes, [Ru(vbpy)3]2+ and [Os(vbpy)3]2+ (vbpy = 4-methyl-4/-vinyl-2,2/-bipyridine), have excited state lifetimes of approximately 900 and 60 ns, respectively. Incorporation into the sol-gel pores and polymerization (reductive polymerization initiated at the ITO electrode) results in chromophores that exhibit a remarkably small amount of self-quenching and have domains that reflect relatively isolated chromophores with excited state lifetimes longer than the solution values [125]. 

The HPLC chromatogram containing monomeric and dimeric lignols from spruce wood can be seen in Figure 2. Dual channel UV-detection was used during the HPLC analysis with one channel set at 280 nm to detect all lignin-related products and the other channel at 350 nm to monitor the presence of leucochromophores. Most... 

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