Characteristic amino acid combinations in olfactory G protein‐coupled receptors

Abstract

The human olfactory subgenome has recently been fully characterized with over 1000 genes. Although as many as two thirds of them are expected to be pseudogenes, it still leaves us with about half of all human G protein-coupled receptors being olfactory. It is therefore of great interest to characterize olfactory receptors with high precision. Usually it is done through sequence motifs that are not fully conserved, making an exact characterization difficult. In this paper, we propose a rule-based characterization of olfactory receptors derived from a multiple sequence alignment of human GPCRs. We show that just seven alignment sites are sufficient to characterize 99% of human olfactory GPCRs with one feature, a tyrosine at site 7.41, being of particular importance. We also show dependencies between sites near the extracellular and intracellular region of a membrane-embedded receptor, indicating that olfactory receptors are characterized by a combination of important residues in these two areas, whereas nonolfactory receptors tend to have residues of lower importance at the same sites.

Conserved C‐terminal motifs in odorant receptors instruct their cell surface expression and cAMP signaling

“…26,28 A few studies failed, however, to identify any conserved AA motifs in ORs, 18,[36][37][38] such as "KDEL," "KKxx," or "RxR" sequences that typically are involved in, for instance, ER retention/retrieval or Golgi to ER recycling of integral membrane proteins (Table 1). In sharp contrast, several studies unambiguously pointed out conserved patterns of at least membrane-proximal, basic AAs within the C-termini of ORs, 31,[39][40][41] some of which overlapped with amphiphilic helix 8, a C-terminal structure in many GPCRs that was originally identified in rhodopsin, 42 and later also in ORs. 43,44 We therefore hypothesized, that ORs, like many GPCRs, are indeed equipped with conserved, C-terminal AA motifs, which may be attributable to the ORs' individual or even class-specific plasma membrane expression and/or cAMP signaling.…”

“…59 Moreover, the specific constitution of these motifs is class-specific, for example, the dominant "[+]x[+]" motif at C-term 3-5 , which occurs at high rates in either class, is predominantly a "KxK" in class-I ORs, but a "RxK" or "RxR" in class-II ORs, and has been shown previously to be highly conserved within ORs. 31,40,41 As the variables plot in Figure 1 shows, the major contributors to the differentiation of class-I and class-II ORs are the class-I-specific "[+] x[+]" motif at C-term 8-10 , and the class-II-specific "[+][+]" motif at C-term 12-13 (Figure 1A). As expected, a generalized "[+]x[+]" motif at C-term 3-5 did not add to the differentiation of class-I and class-II ORs.…”

Entropy and Variability: A Second Opinion by Deep Learning

“…Wang et al [ 24 ] predicted the early risk of ophthalmopathy in Graves’ disease patients using EV analyses on a patient’s T cell receptor repertoire. Samsonova et al [ 25 ] used the EV method to understand the role of individual residues in the function of olfactory G protein-coupled receptors. Abascal et al [ 26 ] made their model for residue variability among Arthropoda fit the concepts behind the EV method.…”

N-W Algorithm and ANFIS Modeling on Alignment Similarity of Triplex Capsid Protein of Human Herpes Simplex Virus

“…Brylinski et al [8] described a computational model that can be used to identify potential areas that are able to interact with other molecules (ligand, substrates and inhibitors). Samsonova et al [9] proposed a rule-based characterization of olfactory receptors derived from a multiple sequence alignment of human GPCRs. They concluded that seven alignment sites are sufficient to characterize 99% of human olfactory GPCRs.…”