GPCRs , 7-transmembrane

Topiol, S. and Sabio, M. (2009) X-ray structure breakthroughs in the GPCR transmembrane region. Biochemical Pharmacology, 78 (1), 11-20. 8... 

The conformation and dynamics of a GPCR transmembrane cannabi-noid receptor-1 was studied by solid-state NMR spectroscopy which showed the orientation of the helices. 

The four mammalian ARs are members of the rhodopsin-like Class A family of GPCRs, which contain seven transmembrane helical domains ( TMs). Character istics of the four subtypes of the human ARs, length of their primary sequences, their chromosomal localization, and their signaling pathways are given in Table 1. The A2a receptor is considerably longer than the other three subtypes, due to its extended carboxy-terminal. 

Frizzled (Fz) proteins comprise a family of seven-pass transmembrane receptors with a cysteine-rich extracellular domain. As a class, Fz proteins are structurally related to the superfamily ofheterotrimeric G-protein coupled receptors (GPCRs). Diere are 4 Fz genes in Drosophila and 10 in humans, with close orthologs... 

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... 

Three endogenous opioids have been identified enkephalins, dynorphins and beta-endorphins. These opioid peptides selectively bind to the seven transmembrane GPCRs delta (8), kappa (k), and mu (p). Although dynorphin binds predominately to the k receptor, P-endorphines and enkephalins bind to p and 8 opioid receptors. It is important to note that the analgesia induced by opioids is mediated predominately throngh the p opioid receptor. In vitro studies have shown a decrease in the immnne function and proliferation following p-endorphin administration in rodents (Ray and Cohn 1999) and that the immunosuppressive effects by P-endorphins are steroid-independent (Berkenbosch et al. 1984 Nelson et al. 2000). 

The human oxytocin receptor gene was isolated and characterised in 1994 [122], heralding the development of modern cloned receptor screening. The oxytocin receptor belongs to the Family A series of G-protein coupled 7-transmembrane receptors (GPCRs). A schematic representation of the generic structure of 7TM receptors is shown in Figure 7.3. 

Fig. 6.3 7-Transmembrane GPCR and extra-cellular view of odourant molecule shown in putative binding position hydrophobic and hydrophilic side-chains (O) shown for protein segments 3, 4 and 5 (from Sharon, 1998).

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