7-transmembrane domain receptors

Scheme 28. Synthesis of a diphenylmethylamine library targeted to 7-transmembrane domain receptors.

What do SNMPs do The identification of Apo/SNMPl followed photoaffinity labeling studies that tentatively identified a 69 kDa protein as a pheromone receptor (Vogt et al., 1987) however, a role as pheromone receptor seems highly unlikely because SNMPs appear to associate with most olfactory neurons, and are neither 7-transmembrane domain receptors nor show the diversity expected for ORs. SNMPs certainly show no similarity to the presumed ORs identified in D. melangaster, A. gambiaea and H. virescens (Clyne et al., 1999 Vosshall et al., 1999 Hill et al., 2002 Krieger et al., 2002). If SNMPs are not ORs, what are they ... 

Within two years, the receptor (named CBj) was cloned from rat brain by a group at NIH [29], It was shown to belong to the 7 transmembrane domain receptor family, members of which mediate their activity through GTP-binding proteins. 

Foord, S. M., and Marshall, F. H. (1999). RAMPS Accessory proteins for seven transmembrane domain receptors. Trends Pharmacol. Sci. 20 184-187. 

These receptors are unlike the well-characterised rhodopsin-like family in that they have a large extracellular N-terminus and hormone binding seems to be dominated by this domain rather than the transmembrane domains. Receptors in this class include... 

FIGURE 18-10 Serpentine (seven-transmembrane-domain) receptors for peptides have binding for their peptide ligands within the membrane... 

Cao, J., Panetta, R., Yue, S., Steyaert, A., Young-BelKdo, M. and Ahmad, S. (2003) A naive Bayes model to predict coupling between seven transmembrane domain receptors and G-proteins. Bioinformatics 19, 234-240. 

Greco NJ, Tandon NN, Jones GD, Komhauser R, Jackson B, Yamamoto N, Tanoue K, Jamiescm GA. Contributions of glycoprotein Ib and the seven transmembrane domain receptor to increases in platdd cytoplasmic [Ca2+] induced by alpha- thrombin. Biochemistry 1996 35 906-14. 

Thrombin will be used as an example of an activator of a seven transmembrane domain receptor. Uptm activation of the receptor, the Gi irotein splits into G and Gp, which both can activate PLCp (Exton, 1994 Brass et al, 1997). Q leads to phosphoinositide hydrolysis and formation of DAG and IP, which activates PKC and en ty C -stores in the endoplasmatic reticulum, respectively. The rise in [Ca causes tyrosine phosfdioi aticHi of the related acbesion focal tyrosine kinase (RAITK.) by an unidentified tyrosine kinase (TK) (Raja et al, 1997). RAFTK can also be tyrosine phosphoiylated by an unknown tyiosiiie kinase (TK.) and activated when PKC is stimulated by phoibol esters... 

Prostanoids act both in an autocrine fashion on the parent cell and in a paracrine fashion on neighboring cells [1,11]. Typically, the role of a prostanoid is to coordinate the responses of the parent cells and neighboring cells to the biosynthetic stimulus — a circulating hormone. The actions of prostanoids are mediated largely by G-protein-linked prostanoid receptors of the seven-transmembrane domain receptor superfamily [11]. 

The mechanism of activation of the receptor-type guanylate cyclases is not entirely clear. As is the case with other single-transmembrane domain receptor types, such as receptor-type tyrosine kinases, some sort of dimerization may be induced by ligand binding, which serves to activate the intracellular enzyme part of the receptor. As discussed in the next section, dimerization is essential to enzyme activity in soluble guanylate cyclases. 

Loetscher, M., Geiser, T., O Reilly, T., Zwahlen, R., Baggiolini, M., and Moser, B. (1993) Cloning of a human seven transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J. Biol. Chem. 269, 232-221. 

CBj and CB receptors are members of the superfamily of the seven transmembrane domain receptors that transduce intracellular signals via heterotrimeric GTP-binding proteins. The CB receptor exhibits low amino acid sequence homology with the CBj receptor (44%). Within the transmembrane regions the sequence identity increases to 68%. The CBj receptor is larger than CB, with an additional 72 amino acid residues in the N-terminal region, 15 additional residues in the third extracellular loop, and 13 in the C-terminal region. 

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