G-protein-coupled receptor interacting

Lazareno, S., and Birdsall, N. J. M. (1995). Detection, quantitation, and verification of allosteric interactions of agents with labeled and unlabeled ligands at G protein-coupled receptors Interactions of strychnine and acetylcholine at muscarinic receptors. Mol. Pharmacol. 48 362-378. 

Brady, A. E. and Limbird, L. E. (2002) G protein coupled receptor interacting proteins emerging roles in localization and signal transduction. Cell. Signal. 14, 297-309. 

The G proteins with which G protein-coupled receptors interact are heterotrimeric complexes composed of a, P, and y subunits. In its inactive state, the G-protein a subunit is bound to GDP and associates with a Py dimer. Upon receptor activation, the a subunit opens its guanine nucleotide binding site and releases its bound GDP, allowing GTP, which is present in higher concentrations in the cell, to bind in its place. The GTP-bound a subunit has a lower affinity for the Py dimer and dissociates from it, freeing both the a sub-... 

Premont RT, Hall RA. 2002. Identification of novel G protein-coupled receptor-interacting proteins. Methods Enzymol... 

The G-proteins are heterotrimers made of three families of subunits, a, P, and y, which can interact specifically with discrete regions on G-protein-coupled receptors. This includes most receptors for neurotransmitters and polypeptide hormones (see Neuroregulators). G-protein-coupled receptors also embrace the odorant receptor family and the rhodopsin-linked visual cascade. 

One target type for which the molecular mechanism of efficacy has been partly elucidated is the G-protein-coupled receptor (GPCR). It is known that activation of GPCRs leads to an interaction of the receptor with separate membrane G-proteins to cause dissociation of the G-protein subunits and subsequent activation of effectors (see Chapter 2). For the purposes of binding, this process can lead to an aberration in the binding reaction as perceived in experimental binding studies. Specifically, the activation of the receptor with subsequent binding of that... 

Christopoulos, A. (2000). Quantification of allosteric interactions at G-protein coupled receptors using radioligand assays. In Current protocol in pharmacology, edited by Enna, S. J., pp. 1.22.21-1.22.40. Wiley and Sons, New York. 

Several nonconventional cadherins that contain cadherin repeats have been described but they have specific features not found in the classical cadherins [1]. The cadherin Flamingo, originally detected in Drosophila, contains seven transmembrane segments and in this respect resembles G protein-coupled receptors. The extracellular domain of Flamingo and its mammalian homologs is composed of cadherin repeats as well as EGF-like and laminin motifs. The seven transmembrane span cadherins have a role in homotypic cell interactions and in the establishment of cell polarity. The FAT-related cadherins are characterized by a large number of cadherin repeats (34 in FAT and 27 in dachsous). Their cytoplasmic domains can bind to catenins. T- (=truncated-)cadherin differs from other cadherins in that it has no transmembrane domain but is attached to the cell membrane via a glycosylpho-sphatidylinositol anchor. 

Transmembrane Signaling Drag-receptor Interaction G-protein-coupled Receptors Histaminergic System Adenosine Receptois... 

Alike any other G-protein coupled receptors (GPCRs), mGlu receptors have seven transmembrane helices, also known as the heptahelical domain (Fig. 2). As observed for all GPCRs, the intracellular loops 2 and 3 as well as the C-terminal tail are the key determinants for the interaction with and activation of G-proteins. However, sequence similarity analysis as well as specific structural features make these mGlu receptors different from many other... 

Muscarinic acetylcholine receptors (mAChRs) form a class of cell surface receptors that are activated upon binding of the neurotransmitter, acetylcholine. Structurally and functionally, mAChRs are prototypical members of the superfamily of G protein-coupled receptors. Following acetylcholine binding, the activated mAChRs interact with distinct classes of heterotrimeric G proteins resulting in the activation or inhibition of distinct downstream signaling cascades. 

The 3 isozymes are activated by G protein-coupled receptors through two different mechanisms [2]. The first involves activated a-subunits of the Gq family of heterotrimeric G proteins (Gq, Gn, Gi4, G15/16). These subunits activate the (31, (33 and (34 PLC isozymes through direct interaction with a sequence in the C terminus. The domain on the Gqa-subunit that interacts with the (3 isozymes is located on a surface a-helix that is adjacent to the Switch III region, which undergoes a marked conformational change during activation. The second mechanism of G protein activation of PLC 3 isozymes involves (3y-subunits released from Gi/0 G proteins by their pertussis toxin-sensitive activation by certain receptors. The 3y-subunits activate the 32 and 33 PLC isozymes by interacting with a sequence between the conserved X and Y domains. 

Drug Interactions Drug-Receptor Interaction G-protein-coupled Receptors Tolerance and Desensitization Transmembrane Signaling... 

Harrison JK, Barber CM, Lynch KR (1994) cDNA cloning of a G-protein-coupled receptor expressed in rat spinal cord and brain related to chemokine receptors. Neurosci Lett 169 85-89 Harrison JK, Jiang Y, Chen S et al (1998) Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci USA 95 10896-10901... 

Heterologous desensitisation refers to the desensitisation of the response to one agonist by the application of a different agonist. For example, desensitisation of a response to adrenaline by application of 5-HT is mediated by protein kinase A or protein kinase C because these kinases can phosphorylate receptors which are not occupied by agonist. Phosphorylation disrupts the receptor-G-protein interaction and induces the binding of specific proteins, arrestins which enhance receptors internalisation via clathrin-coated pits. Thus desensitisation of G-protein-coupled receptors results in a decrease in the number of functional receptors on the cell surface. 

Milligan, G. and White, J. H., Protein-protein interactions at G-protein-coupled receptors, Trends Pharmacol. Sci., 22(10), 513-518, 2001. 

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