Odorant receptors sequence

FIGURE 50-3 Amino acid sequence conservation across mammalian odorant receptors. ORs pass through the plasma membrane (blue box) seven times, with the AT-terminus located extracellularly and the C-terminus intracellularly. The degree of conservation of each amino acid in this consensus OR is indicated by a colored ball, with dark blue being most highly conserved and red most highly variable. Modified from [5], with permission. 

Odorants are thought to bind to integral membrane receptors on the cilia of the olfactory sensory neurons. The receptors are thought to he specific different olfactory neuron types recognize different odorants that share certain characteristics (Buck, 1993). The odorant receptors transduce signals via interactions with G-proteins (so-called because guanosine trisphosphate is involved in their activation). These G-protein-coupled exhibit seven hydrophobic domains (Fig. 5.6). Variation in the amino acid sequence of the transmembrane domain may account for specificity and selectivity of odor reception. 

The OR proteins are typically 20% identical in sequence to the P-adrenergic receptor (Section 15.1) and from 30 to 60% identical with each other. Several specific sequence features are present in most or all OR family members (Figure 32.4). The central region, particularly transmembrane helices 4 and 5, is highly variable, suggesting that this region is the site of odorant binding. That site must be different in odorant receptors that bind distinct odorant molecules. 

Of mice and rats. As noted in Section 32.1.2. one of the first odorant receptors to be matched with its ligand was a rat receptor that responded best to -octanal. The sequence of the corresponding mouse receptor differed from the rat receptor at 15 positions. Surprisingly, the mouse receptor was found to respond best to n-heptanal rather than n-octanal. The substitution of isoleucine at position 206 in the mouse for valine at this position in the rat receptor was found to be important in determining the specificity for n-heptanal. Propose an explanation. 

Young JM, Shykind BM, et al. (2003) Odorant receptor expressed sequence tags demonstrate olfactory expression of over 400 genes, extensive alternate splicing and unequal expression levels. Genome Biol 4(11 ) R71... 

Nguyen MQ, Zhou Z, Marks CA, Ryba NJ, Belluscio L (2007) Prominent roles for odorant receptor coding sequences in allelic exclusion.Cell 131 (5) 1009—1017 Nishizumi H, Kumasaka K, Inoue N, Nakashima A, Sakano H (2007) Deletion of the core-H region in mice abolishes the expression of three proximal odorant receptor genes in cis.Proc Natl Acad Sci USA 104(50) 20067-20072... 

After the discovery of odorant receptors (ORs) by Buck and Axel in 1991 the identification of the receptors responsible for vomeronasal chemodetection was thought to represent a relatively easy task (Buck and Axel 1991). This was not the case, however, as although vomeronasal receptors (VRs) (like ORs) are putative seven-transmembrane receptors, they do not share any sequence similarity with ORs. 

Odorant receptor molecules belong to the family of G protein-coupled receptors with seven transmembrane domains they were cloned by polymerase chain reaction (PCR) using primers homologous to two sequence regions highly conserved between dif-... 

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