Transmembrane regions

This enigma was resolved in 1990 when the x-ray structure of an outer membrane protein, porin, showed that the transmembrane regions were p... 

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

Inward Rectifier K+ Channels. Figure 5 Proposed three-dimensional arrangement of the transmembrane region of Kir channels. Two of four subunits are indicated. The pore consists of a selectivity filter close to the outside part of the membrane, a central inner vestibule, and a cytoplasmic entrance. Spermine may block in the inner cavity or in the selectivity filter. Large intracellular vestibule where polyamines may also block the channel is not shown. 

Cell membrane spanning proteins contain a luminal/ extracellular domain, a transmembrane region and a cytosolic domain. In a type I transmembrane protein the N-terminus is the extracellular/luminal part of the protein, whereas the C-terminus comprises the cytosolic region of the membrane protein. 

Figure 11.7 Presumed arrangement of GABAa receptor subunits to form a receptor-channel complex, (a) Diagrammatic representation of an individual subunit with four transmembrane regions, extracellular sites for glycosylation and a site for phosphorylation on the intracellular loop between M3 and M4. (b) Association of five subunits to form a central ionophore bounded by the M2 region of each subunit. The suggested stoichiometry of the most widely expressed form of receptor is 2a, 2 and ly. Shown below are the possible subunit combinations of one such benzodiazepine-sensitive receptor together with a benzodiazepine-insensitive receptor in which the 7 subunit is replaced by a c5, and a ti-containing receptor with four different subunit types...

Fig. 2. The hypothetical structure of Ca -ATPase. The structure consists of three major cytoplasmic domains, a pentahelical stalk region, and an intramembranous domain with ten, presumably helical, transmembrane segments. Ti and T2 mark the tryptic cleavage sites. Inset charged amino acids in and near the transmembrane region that may contribute to a Ca " -channel. Adapted from Brandi et al. [8].

The 4TM receptors are pentameric complexes composed of subunits of 420 to 550 amino acids. The subunits exhibit sequence identities from 25 to 75%, with a similar distribution of hydrophobic and hydrophilic domains (Table 3.1). The hydrophilic 210 to 230 amino-acid N-terminal domain is followed by three closely spaced hydrophobic and putative transmembrane domains, then a variable-length intracellular loop, and finally a fourth putative transmembrane region shortly before the C-terminus (Figure 3.1). Of the four candidate transmembrane regions, evidence suggests that TM2 forms an a-helix, while the other hydrophobic regions more likely are folded as (3-sheets. 

Extracellular ATP has been demonstrated to activate a depolarizing current in different neuronal and non-neuronal cell types. These receptors are also referred to as P2 receptors. The receptors can further be divided into the G-protein-coupled P2Y receptors and the ligand-gated ion channels P2X. Currently, seven P2X receptors (P2XJ-P2X- ) have been cloned (Table 3.3). The receptors exhibit between 26 and 50% overall amino-acid identities, with the highest level of conservation in the extracellular and transmembrane regions. P2X7 (also called P2Z) is the most distant member of the family. 

The receptors range in size from 379 to 595 amino acids. The receptors have two transmembrane regions with intracellular N- and C-termini (Figure 3.11). Extensive SCAM analysis suggests that TM2 forms the pore, and a conserved glycine residue in the middle of TM2 lines the narrowest part of the channel. The structure of the pore and the location of the gate have still not been... 

The 5-HTy receptor is part of the G-protein superfamily of receptors, which contains seven transmembrane regions, and its stimulation leads to an increase in cAMP production (Thomas Hagan, 2004). The 5-HT7 receptor is expressed in a number of telencephalic, diencephalic, mesencephalic, and rhombencephalic areas (Table 9.8). 

Figure 2.1 Diagram of nicotinic acetylcholine receptor (nAChR) structure. A top view of (A) an a7 nAChR and (B) a p2 nAChR shows that homomeric and heteromeric classes of nAChRs are both pentameric in structure. Each subunit is made up of four transmembrane domains with the M2 domain making up the ion pore. (C) A side view of the four transmembrane regions shows the N terminus, C terminus, and large M3-M4 intracellular loop that make up each nAChR subunit. The extracellular loops are available for binding to ligands and the intracellular loop is available for regulation of the nAChR by intracellular signaling proteins.

Staphylococcus carnosus is genetically highly stable, a good secretor (Gram positive) able to translocate proteins containing several hydrophobic transmembrane regions [58], and it has no extracellular proteases, which makes it suitable for production of the secreted enzymes [58],... 

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