Seven-transmembrane “-helical motif

Fig. 4 A molecular model of the dopamine D2 receptor with a ligand docked in the binding site. The model of the D2 receptor transmembrane helices was constructed from the coordinates of the bacteriorhodopsin structure derived from two-dimensional electron diffraction experiments and is consistent with the projection structure for rhodopsin. The transmembrane helices are represented by a solid ribbon and the drug, apomorphine, is a space filling representation. The top view looking down the helical axis of the receptor clearly delineates the seven transmembrane helices that are the key structural motif for the GPCR superfamily. Some of the helices are inclined relative to the perpendicular to the membrane plane. The bottom view is in the plane of the membrane with the extracellular space at the top of the figure. (Adapted from Ref.t f)...

Seven transmembrane helices (7-TM) are a stmctural motif common to a large family of photo- and chemoreceptor proteins. Most prominent examples of 7-TM proteins include (bacterial) rhodopsins and G protein-coupled receptors (GPCRs). 

Fig. 2. Structure of a heptahelical receptor. Cartoon model of dark (inactive) bovine rhodopsin (1U19), showing the seven transmembrane-spanning a helices (red to blue) and 11-r/Vi ctinal (gray spheres). Conserved residues important for receptor and G protein activation are shown (magenta spheres), including the DRY motif on helix III (yellow) and NpxxYx5F motif on helices VII and VIII blue and purple). The extracellular and intracellular faces of rhodopsin are shown. Receptor activation results in an outward movement of helix VI yellow arrow), which opens a gap in the cytoplasmic face of the receptor, exposing residues critical for G protein activation, such as the DRY motif on helix III (yellow).

Despite the broad range of possible actions of GPCRs, they all share a common seven a-helical transmembrane motif of the structure. The ligand binding site is located either at the extracellular region or within the transmembrane a-helical bundle, and the cytoplasmic loops are responsible for coupling to G proteins and activate them (GPCRs act in an enzymatic way) whereas other proteins like arrestins stop enzymatic action of these receptors. 

Fig. 5. Topology and common structural features of GPCRs from class A. The characteristic seven transmembrane domains, which are presumably a-helical, are shown as numbered cylinders TMI-VII. These are connected by intracellular loops ICLI-III and extracellular loops, ECLI-III. A conserved disulfide links ECLI and ECLII. The residues that define common sequence motifs, as discussed in the text, are denoted by white circles. Post-translational glycosylation and palmitoylation modifications are depicted at the N- and C-termini, respectively (see text for additional discussion and references).

FIGURE 1 This cartoon illustrates the secondary structure typical of a CC chemokine receptor. The seven-transmembrane (TM) helices in the bundle are depicted as cylinders and are held together by disulphide bonding of conserved cysteine residues (yellow). The N-terminus is negatively charged and binds the predominantly basic chemokine, while the intracellular C-terminus is rich in serine and threonine residues, some of which undergo phosphorylation following receptor activation. The DRY motif of TM helix 3 is also illustrated. 

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