Seven transmembrane helices

Figure 12.3 Two-dimensional crystals of the protein bacteriorhodopsin were used to pioneer three-dimensional high-resolution structure determination from electron micrographs. An electron density map to 7 A resolution (a) was obtained and interpreted in terms of seven transmembrane helices (b).

Figure 12.S Schematic diagram of the bacteriorhodopsin molecule illustrating the relation between the proton channel and bound retinal in its tram form. A to E are the seven transmembrane helices. Retinal is covalently bound to a lysine residue. The relative positions of two Asp residues, which are important for proton transfer, are also shown. (Adapted from R. Henderson et al.,...

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. 

Heptahelical domains are protein modules found in all known G-protein coupled receptors, made up of seven transmembrane helices interconnected by three extra and three intracellular loops. For most G-protein coupled receptors activated by small ligands, the binding site is located in a cavity formed by transmembrane domains 3, 5, 6 and 7. 

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... 

Most of the G-protein-coupled receptors are homologous with rhodopsin however, other quantitatively minor families as well as some individual receptors do not share any of the structural features common to the rhodopsin family (Figure 2.3). The most dominant of these are the glucagon/VIP/caldtonin receptor family, or family B (which has approximately 65 members), and the metabotropic glutamate receptor family, or family C (which has approximately 15 members), as well as the frizzled/smoothened family of receptors. Thus, the only structural feature that all G-protein-coupled receptors have in common is the seven-transmembrane helical bundle. Nevertheless, most non-rhodopsin-like receptors do have certain minor structural features in common with the rhodopsin-like receptors — for example, a disulfide bridge between the top of TM-III and the middle of extracellular loop-3, and a cluster of basic residues located just below TM-VI. 

FIGURE 7.3 Superposition of the seven transmembrane helices (numbered 1-7) of a GPCR on the outer surface of a G-protein. Abbreviations CT, C-terminus NT, N-terminus icl, ic2, and ic3, first, second, and third intracellular loops of the GPCR. (From Bourne, H. R., Curr. Opin. Cell. Biol., 9, 134, 1997. With permission.)... 

Fig. 27. A schematic representation of the seven transmembrane helical peptide chains (A-G) viewed from inside the cell. The numbering denotes the first and last amino acid residues. The proton channel is believed to be the volume between helices C, D, F and G...

Ovchinnikov 234 237) has shown that bovine rhodopsin, although quite different in amino acid sequence (348 residues), also forms seven transmembrane helices. This structural similarity between bacterial and mammalian light activated membrane proteins is remarkable. Since the two amino acid sequences have little in common it would appear that the necessary requirement is seven transmembrane helices to form a channel which is specific for proton migration. For example it has been suggested that a similar arrangement and function is performed by the lactose permease of E. coli237). 

In this context, we focus on G-protein coupled receptors (GPCRs) with seven transmembrane helices (TMHs) that act as the gateway for signal transduction at the cell surface membrane. An external ligand stimulus applied to GPGR induces coupling with G-proteins (G , G and G, etc.), followed by... 

Fig. 5.6. Topology of the P-adrenergic receptor of hamster. The primary structure is shown of the P-receptor for adrenaline from hamster, with the assumed topology of the seven transmembrane helices. The extracellular domain is shown at the top of the picture. The interface of the ceU membrane is indicated by the dashed line. The filled squares show glycosylation sites. Amino adds not required for ligand binding, according to mutagenesis studies, are shown as open squares. Reprinted with permission of the American Journal of Respiratory Cell and Molecular Biology (1989), 1, No.2, p.82.

The /3-adrenergic receptor is an integral protein with seven hydrophobic regions of 20 to 28 amino acid residues that snake back and forth across the plasma membrane seven times. This protein is a member of a very large family of receptors, all with seven transmembrane helices, that are commonly called serpentine receptors, G protein-coupled receptors (GPCR), or 7 transmembrane segment (7tm) receptors. The binding of epinephrine to a site on the... 

A three-dimensional structure also has been elucidated for bacteriorhodopsin, an integral membrane protein of the halophilic (salt-loving) bacterium Halobacterium halobium. This protein has been studied intensively because of its remarkable activity as a light-driven proton pump (see chapter 14). It forms well-ordered arrays in two-dimensional sheets that can be studied by electron diffraction. Measurements of the diffraction patterns show clearly that bacteriorhodopsin has seven transmembrane helices (fig. 17.12). 

Membrane attached receptor proteins contains seven transmembrane helices (e.g., bacteriorhodopsin, Figure 12.1b). 

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... 

G protein-coupled receptors are a large class of transmembrane receptors. They have seven transmembrane helices. Therefore, they are called heptahelical or serpentine receptors. They bind watersoluble hormones, such as adrenaline but also peptides and accept sensory signals, light, odorants and some taste stimuli. On binding the ligand they transmit the signal to heterotrimeric, a,p,y-G proteins. 

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