G Protein-coupled Receptors

Ji, Tae H.; Grossmann, Mathis; Ji, Inhae

doi:10.1074/jbc.273.28.17299

Cited by 641 publications

(289 citation statements)

References 48 publications

(57 reference statements)

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“…The binding pocket of the receptor is thought to be located approximately 9 A beneath the membrane surface [17] and its functional viability very likely requires the proper arrangement of the seven transmembrane a-helices. The retention of binding suggests that neither the reconstitution procedure nor the presence of the underlying hydrogel support caused significant distortion of protein folding, at least when the receptor was protected with carbachol during reconstitution.…”

Section: Resultsmentioning

confidence: 99%

Characterization of radioligand binding to a transmembrane receptor reconstituted into Lipobeads

Park

Buck

et al. 2004

FEBS Letters

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Lipobeads are hydrogel beads surrounded by a lipid bilayer membrane and have been developed to act as a cell analogue. The FLAG-tagged M 2 muscarinic receptor was incorporated onto the surface of the Lipobead by incubating pre-Lipobeads with proteoliposomes containing the receptor. Receptors reconstituted onto the surface of the Lipobeads were functional in that they bound the antagonists quinuclidinylbenzilate and scopolamine with characteristic muscarinic affinities. This demonstrates the feasibility of using Lipobeads to study the binding properties of the M 2 muscarinic receptor and offers a promising approach to the study of transmembrane protein biology in general.

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Section: Resultsmentioning

confidence: 99%

Characterization of radioligand binding to a transmembrane receptor reconstituted into Lipobeads

Park

Buck

et al. 2004

FEBS Letters

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“…The diversity of ligands activating GPCRs, as different as a photon of light and a 40 kDa protein, is reflected in the variety of mechanisms of ligand binding, such as the simplest mechanism for a ligand to activate a receptor binding the transmembrane core (norepinephrine, serotonin), or the protease ligand thrombin that cleaves the amino terminus of the receptor [21,91].…”

Section: Molecular Mechanism Of Receptor-g Protein Couplingmentioning

confidence: 99%

Heterotrimeric G Proteins: Insights into the Neurobiology of Mood Disorders

González-Maeso

Meana²

2006

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Mood disorders such as major depression and bipolar disorder are common, severe, chronic and often lifethreatening illnesses. Suicide is estimated to be the cause of death in up to approximately 10-15% of individuals with mood disorders. Alterations in the signal transduction through G protein-coupled receptor (GPCR) pathways have been reported in the etiopathology of mood disorders and the suicidal behavior. In this regard, the implication of certain GPCR subtypes such as 2A -adrenoceptor has been repeatedly described using different approaches. However, several discrepancies have been recently reported in density and functional status of the heterotrimeric G proteins both in major depression and bipolar disorder. A compilation of the most relevant research topics about the implication of heterotrimeric G proteins in the etiology of mood disorders (i.e., animal models of mood disorders, studies in peripheral tissue of depressive patients, and studies in postmortem human brain of suicide victims with mood disorders) will provide a broad perspective of this potential therapeutic target field. Proposed causes of the discrepancies reported at the level of G proteins in postmortem human brain of suicide victims will be discussed.

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“…A fourth intracellular loop is formed because a region adjacent to the C-terminal segment is palmitoylated at specific Cys residues. Each of the 7TM helices is, in general, composed of 20-27 amino acids, and connecting loops, and N-and C-terminal domains that vary in size as an indication of the diversity of conformations and functions [10] (see Fig. 2).…”

Section: Structure Of G-protein-coupled Receptors (Gpcrs)mentioning

confidence: 99%

“…Proteolytic studies of Rho and opsin, revealed that the carboxyl-terminal residues play only a minor role the thermal stability of Rho and opsin, whereas the Figure 2. Representation of different receptor-ligand interactions observed within the GPCRs superfamily (adapted from [10]). Different ways have been described for the initial triggering event of receptor activation: (A) Exclusively at the transmembrane core, like retinal activation by light in the case of Rho, and ligands such as amines, nucleosides, eicosanoids and lipid moieties; and (B) not only at the transmembrane core but also at extracellular loops and N-terminal segments for peptides of ≤ 40 amino acids.…”

Section: Conformational Stability Of Gpcrsmentioning

confidence: 99%

Stabilization of Membrane Proteins: the Case of G‐Protein‐Coupled Receptors

Reyes‐Alcaraz

Tzanov

Garriga

2008

Engineering in Life Sciences

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G-protein-coupled receptors are integral membrane proteins which constitute the largest family of signal transduction molecules participating in the majority of normal physiological processes. G-protein-coupled receptors are responsible for the control of enzyme activity, ion channels and vesicle transport, and they respond to a wide variety of stimuli, like signals involved in sensory systems such as vision, taste and olfaction, but also to a diverse set of chemical signals such as lipids, hormones, neurotransmitters, amino acids, nucleotides, peptides and proteins. This family of receptors is being widely studied because of its potential use as pharmacological targets in drug development, and recently also for its potential use in the development of novel biosensors. G-protein-coupled receptors are specifically designed to fold and function in a lipid bilayer environment, where these membrane proteins are remarkably stable and achieve their optimal performance. The currently used technology for the purification of G-protein-coupled receptors consists in their extraction from the cell membrane and solubilization into detergent micelles. A common drawback of this strategy is that G-proteincoupled receptors solubilized in typical detergents show rather poor conformational stability, which may result in relatively rapid inactivation. The poor stability of detergent-solubilized samples renders many membrane proteins biochemically intractable. This precludes the determination of a high-resolution structure and imposes severe limitations for the development of applications. Thus, the enhancement of the stability of G-protein-coupled receptors is a major issue in order to facilitate structural determination and to unravel their potential in biotechnological applications. This work provides a brief overview of some current advances in the experimental methods for stabilizing G-protein-coupled receptors that can also be extended to other types of membrane proteins. Structure of G-protein-Coupled Receptors (GPCRs)The distinctive structural feature of GPCRs is the bundle of seven transmembrane (7TM) a-helices that constitutes a relevant signature in structural biology. This conformational architecture, and its functional implications, is central to pharmacology and therapeutics. Nearly 2000 GPCRs have been reported since bovine opsin was cloned in 1983 and the b-adrenergic receptor in 1986. They are classified into over 100 subfamilies as a function of their sequence homology, ligand structure and receptor function. Significant differences exist among the members of the GPCRs superfamily, in spite of the high degree of amino acid homology found among the members of a particular subfamily. The visual photoreceptor rhodopsin (Rho) was the first GPCR whose crystal structure was determined at high-resolution [1][2][3][4][5][6][7]. The natural abundance and availability of Rho has made of this protein the prototypical GPCR for structural studies. As a consequence, Rho is often selected as a model protein for biochemical and b...

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G Protein-coupled Receptors

Cited by 641 publications

References 48 publications

Characterization of radioligand binding to a transmembrane receptor reconstituted into Lipobeads

Characterization of radioligand binding to a transmembrane receptor reconstituted into Lipobeads

Heterotrimeric G Proteins: Insights into the Neurobiology of Mood Disorders

Stabilization of Membrane Proteins: the Case of G‐Protein‐Coupled Receptors

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