Membrane-embedded receptors

Barrantes, F. J., Antollini, S. S., Blanton, M. R, and Prieto, M. 2000. Topography of the nicotinic acetylcholine receptor membrane-embedded domains. /. Biol. Chem. 275 3733. —37339. 

The interest in vesicles as models for cell biomembranes has led to much work on the interactions within and between lipid layers. The primary contributions to vesicle stability and curvature include those familiar to us already, the electrostatic interactions between charged head groups (Chapter V) and the van der Waals interaction between layers (Chapter VI). An additional force due to thermal fluctuations in membranes produces a steric repulsion between membranes known as the Helfrich or undulation interaction. This force has been quantified by Sackmann and co-workers using reflection interference contrast microscopy to monitor vesicles weakly adhering to a solid substrate [78]. Membrane fluctuation forces may influence the interactions between proteins embedded in them [79]. Finally, in balance with these forces, bending elasticity helps determine shape transitions [80], interactions between inclusions [81], aggregation of membrane junctions [82], and unbinding of pinched membranes [83]. Specific interactions between membrane embedded receptors add an additional complication to biomembrane behavior. These have been stud-... 

Figure 13.2 Activated G protein receptors, here represented as seven red transmembrane helices, catalyze the exchange of GTP for GDP on the Gapy trimer. The then separated Ga-GTP and Gpy molecules activate various effector molecules. The receptor is embedded in the membrane, and Ga, Gpy and G py are attached to the membrane by lipid anchors, and they all therefore move in two dimensions. (Adapted from D. Clapham, Nature 379 297-299, 1996.)...

Since receptors are embedded in cell membranes it is more convenient to consider the amount of receptor either free or bound as a proportion of the total receptor present. The proportion of receptors in state R (free) is... 

One important class of these systems is the membrane embedded enzyme-receptors such as tyrosine kinases. The binding of the extracelullar agonists... 

It is obvious why the spectroscopist wants to investigate the structure of integral membrane proteins or enzymes, whose biological action is linked to the presence of phospholipids such as phospholipase, in a membrane-mimicking environment Why such an environment should also be used for other peptides like hormones becomes more clear when we take into account the membrane compartment theory [10-12] as postulated by R. Schwyzer. This theory states that peptides that target membrane-embedded receptors... 

Receptor protein embedded in the cell membrane, the active site of the receptor opens on the outside region of the cell. 

One of the most unique and powerful features of steroid hormones is the nature of the steroid receptor. Unlike most other hormones or drugs, which target protein receptors usually embedded in membranes, steroids target the genes themselves, buried deep within the nucleus of the cell. 

FIGURE 10. A) Schematic of taste cell embedded in epithelium. Shown are the apical membrane which contains the microvilli and the basal membrane which synapses with the nerve B) Stimulus can interact with a receptor protein embedded in membrane which activates G-protein, with the membrane or directly with an ion channel protein C) GTP stimulation of phosphatase for formation of cAMP or IP3 and opening of ion channel (Adapted from ref. 2). 

The picture that has emerged from these studies is of an initial interaction of a stimulus with a matched portion of a receptor protein embedded in the cell membrane (13,65). This initial interaction causes stimulation of the linked G-protein to form cGMP. This is coupled to the reactivity of adenylate cyclase in the cells, leading to increased levels of cAMP, which opens ion channels in the cell membrane. A similar sequence can alternatively activate inositol phosphate as a second messenger. Either odorants, cAMP or cGMP can cause a potential change in the membrane (13,70,71,72). As in hormone-sensitive and neurotransmitter-... 

Amphetamines not only mimic the action of norepinephrine and dopamine they also boost the levels of these neurotransmitters in a synaptic cleft by blocking their removal. Normally, neurotransmitters are reabsorbed by presynaptic neurons after they have exerted their effect on postsynaptic receptor sites. This process, commonly called neurotransmitter reuptake and illustrated in Figure 14.24, is the body s way of recycling neurotransmitters, molecules that are difficult to synthesize. Special membrane-embedded proteins are required to pull once-used neurotransmitter molecules back into a presynaptic neuron. Amphetamines inactivate norepinephrine and dopamine reuptake proteins by binding to them. As a consequence, the concentration of these stimulating neurotransmitters in the synaptic cleft is maintained at a higher-than-normal level. 

The rhodopsin structure places the il loop adjacent to the short eighth membrane-embedded a-helix. With the exception of the 5-HT4A receptor (six residues), the 5-HT receptors have the same length as the rhodopsin loop (seven residues). Interestingly a XKKLXXX motif is conserved between the rhodopsin sequence and the majority of the 5-HT sequences, suggesting that the il loops of rhodopsin and the 5-HT receptors could have a common structure. Systematic mutagenesis studies have not been conducted. 

Williamson PT, Verhoeven A, Miller KW, Meier BH, Watts A. The conformation of acetylcholine at its target site in the membrane-embedded nicotinic acetylcholine receptor. Proc. Natl. Acad. Sci. U.S.A. 2007 104 18031-18036. 

STD NMR studies have also been performed on membrane-bound receptors by embedding the protein in the phospholipid bilayer of a liposome (166). 

When a stimulus depolarises the transmembrane potential in a spiking axon above the threshold level, an all-or-none action potential in a spiking axon is activated. The action potential propagates unattenuated to the nerve terminal where ion fluxes activate a mobilisation process leading to transmitter secretion.3 The neurotransmitter binds reversibly to receptor proteins embedded in the membrane of a neuron, which triggers a certain effect. There are two types of receptors known, presynaptic receptors or autoreceptors which are present on the neurotransmitter releasing neurons , and postsynaptic or heteroreceptors, which are present on the neurotransmitter receiving neuron . The former are supposed to perform a feed-back function, and slow down the release of neurotransmitter from these neurons when they are stimulated.4... 

Fig. 16 a-d Schematic representation of polymer nanoreactors, a Cross section of triblock copolymer vesicle, b Polymersome with encapsulated enzyme and membrane-embedded channel protein. In the case described in the text, the substrate entering the vesicle is ampicillin, and the product of the hydrolysis is ampicillinoic acid, c Polymersome with embedded ionophores allowing Ca2+ ions to enter the vesicle ere they react with phosphate ions to form calcium phosphate crystals, d The LamB protein serves as a receptor to the 1 phage virus which can inject its DNA through the channel into the polymersome [259]. Reproduced with permission of The Royal Society of Chemistry... 

Some proteins help cells communicate with each other. Insulin is a protein made in the pancreas. After a meal, insulin signals the body s cells to take in and use glucose from the blood. It does this by binding to receptor proteins embedded in the membranes surrounding the cells. 

Information is conveyed within individual neurons by electrical means - generating nerve impulses which can be recorded and displayed on an oscilloscope. In the twentieth century it was shown that information is conveyed between neurons by chemical means. When a nerve impulse (an action potential) travelling along the long extension or axon of a neuron arrives at a junction (or synapse) with another neuron, it causes the release of a neurotransmitter chemical from the presynaptic cell. This chemical affects the electrical properties of the postsynaptic neuron through its interaction with specialized receptor proteins embedded in the surface membrane of the postsynaptic cell. It has been shown that there are numerous kinds of neurotransmitter chemical which, depending on the specific... 

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