Elements of GPCR Structure

GPCRs are integral membrane proteins that, at least in the vast m ority of cases, possess seven transmembrane o-heUces (TM) alternating in their orientation as the protein sequence traverses the membrane (Fig. 5). The N-terminus is extracellular while the G-terminus is cytoplasmic, and the seven transmembrane helices are linked by three extra-cellular loops (EGL) and three intra-cellular loops (IGL) (Gether, 2000 Sakmar, 2002). These loops are important contact regions for ligands in the extracellular compartment and for heterotrimeric G proteins in the intracellular compartment (Kraft et al, 2001 Miettinen et al, 1999 Xie et al, 1997). Additional 

One of the more striking elements of sequence conservation is the Glu/ Asp-Arg-Tyr sequence found at the cytoplasmic interface of TM III (Fig. 5). This so-called (E/DRY) motif is actually E-R-Y in 

Another conserved feature of class A GPCRs is a post-translational addition of two palmitate moieties covalently coupled via thioester bonds to the C-terminal tail at a Cys-Cys motif (Fig. 5) (Qanbar et al, 2003). As a result the receptor C-terminus associates with the membrane creating, in 

These structural features help to define class A GPCRs and may be important components in the activation mechanism for individual receptors in this class. However, as the structural dynamics of class A receptors are beginning to be studied on a molecular level, important differences are emerging between the functional and structural roles of conserved sequence motifs in different class members. Thus, while the presence of conserved sequence motifs may in some cases help predict the mechanistic features of a novel receptor, careful experimental studies are stiU needed to test such predictions. 

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