Transmembrane topology

Figure 3.4 Transmembrane topology of a 7-TM domain G-protein receptor such as the P-adrenoceptor. Agonist binding is predicted to be within the transmembrane domains. The extracellular structure is stabilised by the disulphide bond joining the first and second extracellular loop. The third intracellular loop is the main site of G-protein interaction while the third intracellular loop and carboxy tail are targets for phosphorylation by kinases responsible for initiating receptor desensitisation...

Figure 3.5 shows diagrammatic illustrations of the transmembrane topology of the G-protein-coupled receptor families. Three main families have been identified ... 

Reliable information about the transmembrane topology of ion transport ATPases can be obtained only by a combination of predictions based on amino acid sequence... 

FIGURE 3.1 Schematic representation of the transmembrane topology of the 4TM receptor family. Only TM2 show an a-helical structure in electron microscopic studies the remaining TM regions may fold in (5-sheet structures. Both the N-terminus (indicated by NH2) and the C-terminus are located extracellularly. The cytoplasmic loops between TM3 and TM4 are variable in size and contain putative phosphorylation sites. 

FIGURE 3.11 Schematic representation of the transmembrane topology of the adenosine triphosphate (ATP) receptors. 

The transmembrane topology of glutamate receptors differs from that of nicotinic receptors 278... 

The amino acid sequences of the glutamate transporters show a high degree of similarity with between 40-60% of amino acid residues identical between subtypes. At present, the three-dimensional (3D) structure of the transporters is unknown and indirect methods based on amino acid sequence hydropathy plots and amino acid accessibility methods have been employed to predict the transmembrane topology of the transporters. Two similar models developed by the groups of Amara (12,13) and Kanner... 

Clark, J. A. (1997) Analysis of the transmembrane topology and membrane assembly of the GAT-1 gamma-aminobutyric acid transporter. J. Biol. Chem. 272,14695-14704. 

Groeger, W. and Koster W. (1998). Transmembrane topology of the two FhuB domains representing the hydrophobic components of bacterial ABC transporters involved in the uptake of siderophores, haem and vitamin B12, Microbiology, 144, 2759-2769. 

Brass, V., Lu, X., Thomssen, R., and Gerlich, W. (1994). Post-translational alterations in transmembrane topology of the hepatitis B virus large envelope protein. EMBO J. 

Seal RP, Leighton BH, Amara SG. 1998. Transmembrane topology mapping using biotin-containing sulfhydryl reagents. Methods Enzymol 296 318-331. 

The adenylyl cyclases are large transmembrane proteins with a complex transmembrane topology. The assumed topology (Fig. 5.22) shows a short cytoplasmic N-termi-nal section followed by a transmembrane domain Ml with six transmembrane sections, and a large cytoplasmic domain Cl. The structural motif is repeated so that a second transmembrane domain M2 and a second cytoplasmic domain C2 can be differentiated. The complicated structure resembles the structure of some ATP-dependent membrane transport systems such as the P glycoprotein. A transport function has not yet been demonstrated for adenylyl cyclase. 

The human genome has genes for three closely related chloride-bicarbonate exchangers, all with the same predicted transmembrane topology. Erythrocytes... 

Yamada, H., Moriyama, Y., Maeda, M., and Futai, M. (1996). Transmembrane topology of Escherichia coli H(+) -ATPase (ATP synthase) subunit a. FEBS Lett. 390, 34-38. 

Search the Web site to predict transmembrane topology of rhodopsin with the following sequence and compare the membrane-spanning regions with the hydrophobicity profiles of ProScale... 

Spier AD, Lummis SC. Immunological characterization of 5-HT3 receptor transmembrane topology. J Mol Neurosci 2002 18(3) 169-178. 

---