Transmembrane organization

The sodium channels consist of a highly processed a subunit (260 kDa) associated with auxiliary p subunits. The pore-forming a subunit is sufficient for functional expression, but the kinetics and voltage dependence of channel gating are modified by the p subunits. The transmembrane organization is shown in Figure 9.5. The a subunit is organized in four... 

Figure 9.5 Transmembrane organization of sodium channel a subunit. Right 3-D structure of the a subunit at 0.2 nm resolution. (From Yu et al., 2005. Reproduced with permission of Blackwell Publishing Ltd.)...

Figure 9.9 Transmembrane organization and regulation of the ubiquitous mammalian plasma membrane Na+/H+ exchanger SLC9A1 by binding of carbonic anhydrase (CAB). (Reprinted with permission from Li et al., 2006. Copyright (2006) American Chemical Society.)...

Fig. 4.7. Structure and transmembrane organization of a typical seven pass" G protein-coupl ed receptor protein.

Fig. 4.11. Structure, transmembrane organization, and functional domains of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel.

The Cyt bIf complex is the only electron transport complex for which the transmembrane organization of all its subunits is established. This membrane-spanning complex that functions as an intermediate electron transport complex between PS II and PS I, and translocates protons across the membrane from the stroma to the lumen, contains 4 proteins Cyt / (33 kDa), Cyt 6-563 (23 kDa), the Rieske Fe-S protein (20 kDa) and the unnamed 17 kDa protein. 

Kast, C.. Canfleld, V., Levenson, R., and Gros, P. (1995) Membrane topology of P-glycoprotein as determined by epitope insertion transmembrane organization of the N-terminal domain of mdr3. Biochemistry, 34 (13), 4402-4411. 

Verapamil (Table 1), the first slow channel calcium blocker synthesized to selectively inhibit the transmembrane influx of calcium ions into cells, lowers blood pressure in hypertensive patients having good organ perfusion particularly with increased renal blood flow. Sustained-release verapamil for once a day dosing is available for the treatment of hypertension. Constipation is a prominent side effect. Headache, dizziness, and edema are frequent and verapamil can sometimes cause AV conduction disturbances and AV block. Verapamil should not be used in combination with -adrenoceptor blockers because of the synergistic negative effects on heart rate and contractile force. 

Figure 13.1 The basic organization of a membrane receptor molecule consists of an extracellular domain, a transmembrane region, and an intracellular domain.

The gene defective in cystic fibrosis codes for CFTR (cystic fibrosis transmembrane condnctance regulator), a membrane protein that pumps CP out of cells. If this CP pump is defective, CP ions remain in cells, which then take up water from the surrounding mucus by osmosis. The mucus thickens and accumulates in various organs, including the lungs, where its presence favors infections such as pneumonia. Left untreated, children with cystic fibrosis seldom survive past the age of 5 years. 

Most ABC-transporters, especially those located in the plasma membrane, are phosphorylated and glycosylated transmembrane proteins of different molecular weights (e.g., P-gp 170 kDa MRP2 190 kDa BCRP 72 kDa). Topologically, most ABC-transporter show a similar structure they are organized in two transmembrane domains (TMD), each consisting of six... 

The structure of all TK receptors is similar in terms of expression oiTACR genes, since all these genes contain five exons intercalated by four introns [1, 5]. Exon I encodes for the N-terminal extracellular tail, the first intracellular (IC1) and extracellular (EC1) loops and the first, second, and third transmembrane domains (TM1, TM2, and TM3). Exon II encodes for the second intracellular (IC2) and extracellular (EC2) loops and the fourth transmembrane domain (TM4). Exon III encodes for the fifth transmembrane domain (TM5) and the third intracellular loop (IC3). Exon IV encodes for the sixth and seventh transmembrane domains (TM6 and TM7) and the third extracellular loop. Exon V encodes for the C-terminal intracellular tail only. A schematic drawing of the amino acid sequences and TK receptor organization is shown in Fig. 1. 

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