M2 channel

Goren EN, Reeves DC, Akabas MH. 2004. Loose protein packing around the extracellular half of the GABAa receptor pi subunit M2 channel-lining segment. J Biol Chem 279 11198-111205. 

S. J. Opella. F. l. Marassi, J. J. Gesell, A. P. Valente, Y. Kim, l. Oblatt-Montal and M. Mental, Structures of the M2 channel-lining segments from nicotinic acetylcholine and NMDA receptors by NMR spectroscopy. Nat. Struct. Biol., 1999, 6, 374-379. 

Pielak RM, Schnell JR, Chou JJ (2011) Mechanism of drug inhibition and drug resistance of influenza A M2 channel. Proc Natl Acad Sci USA 106 7379-7384... 

R 629 Y. Wu and G. A. Voth, Computational Studies of Proton Transport through the M2 Channel , FEES Lett., 2003,552,23 R 630 K. Wuethrich, NMR Studies of Structure and Function of Biological Macromolecules (Nobel Lecture) , Angew. Chem. Int. Ed., 2003,42, 3340... 

H. N. Chen, Y. J. Wu, and G. A. Voth. Proton transport behavior through the influenza A M2 channel Insights from molecular simulation. Biophys. 1, 93 3470-3479, 2007. 

Q. Zhong, T. Hisslein, P.B. Moore, D.M. Newns, P. Pattnaik, and M.L. Klein. The M2 channel of influenza A virus A molecular dynamics study. FEBS Letters, 434 (1998) 265-271. 

The most extreme behavior of the three exemplified sequences is exhibited by the heteropolymer 20.3. The main channel D does not decay in favor of a native-fold channel. In fact, we observe the formation of two separate native-fold channels Mi and M2. Channel Ml advances toward the 0=1 fold and M2 ends up in a completely different conformation with approximately the same energy (E — 33.51). The spatial structures of these two conformations are noticeably different and their mutual overlap is correspondingly very small, 0 0.75. It should also be noted that the lowest-energy conformations in... 

Now, we are in a position to present the relevant extended approximate BO equation. For this purpose, we consider the set of uncoupled equations as presented in Eq. (53) for the = 3 case. The function icq, that appears in these equations are the eigenvalues of the g matrix and these are coi = 2 (02 = —2, and CO3 = 0. In this three-state problem, the first two PESs are u and 2 as given in Eq. (6) and the third surface M3 is chosen to be similar to M2 but with D3 = 10 eV. These PESs describe a two arrangement channel system, the reagent-arrangement defined for R 00 and a product—anangement defined for R —00. 

Ca2+ channel Dopamine Dj Endothelin ETa Endothelin ETb Histamine H2 Muscarinic ml Muscarinic m2 Muscarinic m3 Muscarinic m4 NE transporter Nicotinic Ach NPY,... 

Spiral-wound modules consist of several flat membranes separated by turbulence-promoting mesh separators and formed into a Swiss roll (Figure 16.18). The edges of the membranes are sealed to each other and to a central perforated tube. This produces a cylindrical module which can be installed within a pressure tube. The process feed enters at one end of the pressure tube and encounters a number of narrow, parallel feed channels formed between adjacent sheets of membrane. Permeate spirals roward the perforated central tube for collection. A standard size spiral-wound module has a diameter of about 0.1m, a length of about 0.9 m and contains about 5 m2 of membrane area. Up to six such modules may be installed in series in a single pressure tube. These modules make better use of space than tubular or flat sheet types, but they are rather prone to fouling and difficult to clean. 

Inward Rectifier K Channels. Figure 4 Kir channel subunits consist of two transmembrane domains (M1, M2), separated by a pore loop (P-loop) that contains the signature K+-selectivity sequence (-GYG-), as well as extended cytoplasmic N - and C-termini. Several residues (indicated) have been implicated in causing rectification (see text). 

Stimulation of mAChRs also results in the activation or inhibition of a large number of ion channels [5]. For example, stimulation of Mi receptors leads to the suppression of the so-called M current, a voltage-dependent Recurrent found in various neuronal tissues. M2 receptors, on the other hand, mediate the opening of cardiac Ikcacii) channels, and both M2 and M4 receptors are linked to the inhibition of voltage-sensitive calcium channels [5]. 

The nAChR is comprised of five subunits, each of which spans the lipid bilayer to create a water-filled pore or channel (Fig. la). Each subunit consists of four transmembrane segments, the second transmembrane segment (M2) lines the ion channel (Fig. lb). The extracellular N-terminal domain of every subunit... 

In the resting (closed) state, the ion channel is occluded by a hydrophobic girdle that constitutes a barrier to ion permeation. Agonist binding in the extracellular domain promotes a conformational change that results in a rotational movement of the M2 helices lining the pore, widening the pore by A. This results... 

Molecular biology studies have identified a loop containing 20-25 amino acid residues between S5 and S6 (or Ml and M2, Fig. 2) forming the pore. The G(Y/F) G motif located in the pore represents the K+-selectivity signature, which is common to all K+ channels. The external entry to the channel pore and its adjacent residues constitute binding sites for toxins and blockers. The internal vestibule of the pore and the adjacent residues in S5 and S6 contribute to binding sites for compounds such as 4-aminopyiidine and quinidine. The S4-S5 linker lies close to the permeation pathway and is required for... 

The GABAB-receptors, the muscarinic M2- and IVU-receptors for acetylcholine, the dopamine D2-, D3-and D4-receptors, the a2-adrenoceptors for noradrenaline, the 5-HTiA F-receptors for serotonin, and the opioid p-, 8- and K-receptors couple to G proteins of the Gi/o family and thereby lower [1] the cytoplasmic level of the second messenger cyclic AMP and [2] the open probability ofN- andP/Q-type Ca2+ channels (Table 1). The muscarinic Mr, M3- and M5-receptors for acetylcholine and the ai-adrenoceptors for noradrenaline couple to G proteins of the Gq/11 family and thereby increase the cytoplasmic levels of the second messengers inositol trisphosphate and diacylglycerol (Table 1). The dopamine Dr and D5-receptors and the (3-adrenoceptors for noradrenaline, finally, couple to Gs and thereby increase the cytoplasmic level of cyclic AMP. 

A spiral plate exchanger is illustrated in Figure 9.90 in which two fluids flow through the channels formed between the spiral plates. With this form of construction the velocity may be as high as 2.1 m/s and overall transfer coefficients of 2.8 kW/m2 K are frequently obtained. The size can therefore be kept relatively small and the cost becomes comparable or even less than that of shell and tube units, particularly when they are fabricated from alloy steels. 

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