Transmembrane binding domains

T-cell receptors (TCR) are heterodimeric transmembrane glycoproteins found exclusively in T cells, with extracellular domains that closely resemble antibody Fab structures. Each of the TCR a and p chains forms half of an extracellular antigen-binding domain, and in addition has one transmembrane... 

In the monoamine receptors the ligand-binding domain is located within the transmembrane helices. A pocket is formed between TM3, TM5 and TM6 where the agonist binds. A conserved aspartate residue in TM3 (Asp-113 in the /(-adrenoceptor) and a... 

While the agonist binding domain is thought to be within the transmembrane domains for the monoamine and nucleotide receptors, neuropeptides are thought to bind close to the membrane surface on the extracellular domains of the receptor. It is still not clear whether non-peptide antagonists bind at the same or a different site on the receptor. 

Figure 8.7 Schematic diagram of the proposed structure of the noradrenaline neuronal transporter showing the 12 transmembrane, hydrophobic domains with the N- and C-termini projecting towards the cell cytoplasm. Binding domains for specific ligands are thought to be within regions indicated by the solid bars. (From Stanford 1999, reproduced with permission)...

Unphosphorylated functioning according to Fig. 5 catalyzes facilitated diffusion of mannitol across the membrane. The same process has been reported for purified II reconstituted in proteoliposomes [70]. The relevance of this activity in terms of transport of mannitol into the bacterial cell is probably low, but it may have important implications for the mechanism by which E-IIs catalyze vectorial phosphorylation. It would indicate that the transmembrane C domain of Il is a mannitol translocating unit which is somehow coupled to the kinase activity of the cytoplasmic domains. We propose that the inwardly oriented binding site which is in contact with the internal water phase (Ecyt Mtl, see Fig. 5) is the site from where mannitol is phosphorylated when transport is coupled to phosphorylation. Meehan-... 

This well characterized drug target for anti-asthma medications represents one of the earliest examples of a natural mutation leading to an alteration in ligand binding [20]. Mutation of Thr164 to lie in the fourth transmembrane-spanning domain... 

Ion channels, transporters and many receptors are polytopic. Polar and helix-destabilizing residues are likely to occur within their transmembrane segments to form the requisite gates, channels or binding domains. Transmembrane helices in polytopic proteins are usually... 

The ABC transporters are products of one of the largest gene superfamilies. Each consists of two cytoplasmic nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). The NBDs are highly conserved across the ABC family and contain motifs typical of ATP-binding sites, whereas the TMD structures vary, probably because they are adapted to the wide variety of substrates. In eukaryotes the C-terminal of each NBD is linked to a TMD. In some cases the functional unit is (NBD-TMD)2 and, in others, the first TMD is covalently linked to the second NBD. 

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