Heteromeric odorant receptor, OR (Sato et al., 2008). OR22a senses fruit-derived esters. These olfactory receptors may have 3-d structures resembling animal rhodopsins, human citronellic terpenoid receptors, OR1A1 and OA1A2 and the mouse eugenol receptor, OR-EG (Ramdya and Benton, 2010). Molecular modelling of oligomeric states of DmOR83b has been reported (Harini and Sowdhamini, 2012).  Recombinant receptor together with the co-receptor, Orco, has been overproduced, purified and reconstituted in a lipid bilayer (Carraher et al. 2013).  Orco (Or83b) forms a dimer that is fully functional for Ca²⁺ transport, is regulated by calmodulin and interacts normally with Or22a.  The native Orco is therefore probably a dimer (Mukunda et al. 2014). Fertility decline in female mosquitoes is regulated by the orco olfactory co-receptor (David et al. 2023).  OR46  is a potential sensory receptor associated with host detection in the livestock pest Lucilia cuprina (Wulff et al. 2024).

Insects

Heterometic odorant receptor (OR) of Drosophila melanogaster:
OR83b (Q9VNB5)
OR46a (P81919)
OR43b (P81918)
OR22a (P81909)
OR22b (P81910)

Odorant receptor, OR2 (Carraher et al., 2012) of 378 aas and 7 TMSs.

Insects

OR2 of Anopheles gambiae (Q8WTE6)

Odorant receptor 56a of419 aas and 7 TMSs.  Mediates aversive responses to harmful microbial (bacterial and fungal) products such as geosmin (trans-1,10-dimetnyl-trans-9-decalol). (Stensmyr et al. 2012).

Animals

OR56a of Drosophila melanogaster

Ordorant receptor 67b of 421 aas and 8 TMSs  (Identical to Or67b of D. melanogaster)

Animals (Insects)

Or67b of Drosophila simulans

Odorant receptor 10b of 406 aas and 7 TMSs

Insects

Or10b of Drosophila melanogaster

The insect heteromeric CO₂ receptor: GR21a (Olfactory receptor 21a; 454 aas with 7 or 8 TMSs) GR63a (Olfactory receptor 63a; 512 aas) are coexpressed in antennal neurons of insects and together comprise the peripheral sensory receptor for CO₂ (Ramdya and Benton, 2010). These proteins are members of the 7Tm-7 superfamily of putative 7TMS proteins.

Invertebrate Animals

The gustatory receptor for CO₂, GR21a/GRG3a of Drosophila melanogaster
GR21a (Q9VPT1)
GR63a (Q9VZL7)

Uncharacterized protein of 382 aas and 9 TMSs.

UP of Frankliniella occidentalis (western flower thrips)

Gustatory receptor for sugar taste 64e-like protein, GR64e, of 486 aas and 8 TMSs.

GR64e protein of Atta cephalotes (Leafcutter ant)

Uncharacterized protein of 416 aas and 7 TMSs.

UP of Aphis gossypii (cotton aphid)

Uncharacterized protein of 425 aas and 7 TMSs.

UP of Amphibalanus amphitrite

Gustatory receptor-like (Grl or Gr5a) protein of 444 aas and 8 TMSs. Insect odorant receptors and gustatory receptors define a superfamily of seven- or 8-TMS ligand-gated ion channels (referred to here as 7TMICs), with homologs identified across Animalia, except Chordata, as well as in plants and uncellular eukaryotes (DUF3537 proteins). Several Drosophila melanogaster Grls display selective expression in subsets of taste neurons, suggesting that they are previously- unrecognized insect chemoreceptors. Their origin may be in a eukaryotic common ancestor (Benton and Himmel 2023). It is required for a response to the sugar trehalose in taste neurons (Ueno et al. 2001). Gr5a neurons selectively respond to sugars, in contrast to Gr66a cells which respond to bitter compounds. Flies are attracted to sugars and avoid bitter substances, suggesting that Gr5a neuron activity is sufficient to mediate acceptance behavior. Sugar signal transduction occurs through coupling with G-proteins such as Galpha49B and G-salpha60A.

Grl of Drosophila melanogaster

Gustatory receptor GR64a specific for sugars (sucrose, maltose and glucose). The structures of two sugar GRs have been determined (Ma et al. 2024), the Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBDs, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBDs. Sugar binding to LBDs induces local conformational changes, which are subsequently transferred to the PD to cause channel opening (Ma et al. 2024).

GR64a of

Fructose-regulated Ca²⁺/cation channel, Gustatory (fructose) receptor-9, Gr9 (Sato et al., 2011),which has 8 TMSs in a 5 + 2 + 1 TMS arrangement. Gr9 is widely expressed in the central nervous system (CNS), as well as oral sensory organs and is involved in the promotion of feeding behaviors (Mang et al. 2016). GRs play roles in sensing tastants, such as sugars and bitter substances. The BmGr9 silkworm GR is a d-fructose-gated ion channel receptor. Morinaga et al. 2022 presented a structural model for a channel pore and a D-fructose binding site in BmGr9. Since the membrane topology and oligomeric state of BmGr9 appears similar to those of an insect odorant receptor co-receptor, Orco, they constructed a structural model of BmGr9 based on the cryo-EM Orco structure. Their site-directed mutagenesis data suggested that transmembrane region 7 forms channel pore and controls channel gating. This model also suggested that a pocket formed by transmembrane helices 2-4 and 6 binds D-fructose. They determined the potent binding mode of D-fructose. They proposed a conformational change that leads to channel opening upon D-fructose binding (Morinaga et al. 2022).  Structures of BmGr9, a fructose-gated cation channel, in agonist-free and fructose-bound states have been determined (Frank et al. 2023).  BmGr9 forms a tetramer similar to distantly related insect Olfactory Receptors (ORs). Upon fructose binding, BmGr9's ion channel gate opens through helix S7b movements. In contrast to ORs, BmGR9's ligand-binding pocket, shaped by a kinked helix S4 and a shorter extracellular S3-S4 loop, is larger and solvent accessible in both agonist-free and fructose-bound states. Also unlike ORs, fructose binding by BmGr9 involves helix S5 and a binding pocket lined with aromatic and polar residues. Structure-based sequence alignments revealed distinct patterns of ligand-binding pocket residue conservation in GR subfamilies associated with distinct ligand classes (Frank et al. 2023).

Animals

GR-9 of Bombyx mori (B3GTD7)

Gustatory receptor 43a isoform A.  Functions as a narrowly tuned fructose receptor in taste neurons (Miyamoto et al. 2012), being both necessary and sufficient to sense hemolymph fructose.  The structures of two sugar GRs have been determined (Ma et al. 2024), the Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBDs, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBDs. Sugar binding to LBDs induces local conformational changes, which are subsequently transferred to the PD to cause channel opening (Ma et al. 2024).

Invertebrates

GR43a of Drosophila melanogaster (Q9V4K2)

Gustatory receptor 28b isoform D of 470 aas and 8 TMSs. It mediates acceptance or avoidance behavior, depending on its substrates. Its atypical expression suggests additional nongustatory roles in the nervous system and tissues involved in proprioception (warmth receptor), hygroreception, and other sensory modalities. It is also possible that it has chemosensory roles in the detection of internal ligands (Thorne and Amrein 2008). Saponins function in natural self-defense for plants to deter various insects due to their unpleasant taste and toxicity. Sang et al. 2019 provided evidence that saponin from Quillaja saponaria functions as an antifeedant as well as an insecticide to ward off insects in both the larval and the adult stages.

Invertebrates

GR28b of Drosophila melanogaster (Q9VM08)

Gustatory receptor 2a isoform B

Invertebrates

GR2a of Drosophila melanogaster (Q9W594)

High energy light unresponsive protein 1, Lite1; chemoreceptor GUR-2 of 439 aas and 8 TMSs. It is a photoreceptor for short wavelength (UV) light that mediates UV-light-induced avoidance behavior (Edwards et al. 2008, Liu et al. 2010, Gong et al. 2016). It directly senses and absorbs both UV-A and UV-B light with very high efficiency (Gong et al. 2016). Absorption of UV-B but not UV-A light shows resistance to photobleaching. In contrast to other photoreceptors, it does not use a prosthetic chromophore to capture photons and only depends on its protein conformation. It may play a role in response to white light exposure (De Magalhaes Filho et al. 2018) as well as color detection (Ghosh et al. 2021).

Animals (worm)

GUR-2 of Caenorhabditis elegans

Gustatory receptor, GPRGR53, of 430 aas and 7 TMSs. It mediates acceptance or avoidance behavior, depending on its substrates.

GPRGR53 of Anopheles gambiae (African malaria mosquito)

Putative gustatory receptor 98b of 402 aas and 7 TMSs.

GR98b of Bactrocera latifrons

Gustatory receptor family protein 3, Gur-3, of 447 aas and 8 - 9 TMSs. It is a chemoreceptor involved in light-induced avoidance behavior (Bhatla and Horvitz 2015) and probably acts as a molecular sensor in I2 pharyngeal neurons, required for the inhibition of feeding in response to light and hydrogen peroxide. It may be involved in circadian rhythms, probably by acting as a light sensor (Goya et al. 2016). Although it acts with Lite-1 in color detection, it does not act as a photoreceptor (Ghosh et al. 2021).

Gur-3 of Caenorhabditis elegans

Gustatory receptor Gr66a of 527 aas and 8 TMSs, specific for bitter compounds (Thorne et al. 2004). Gr66a cells respond to bitter compounds such as caffeine, theophylline, threonine or valine. Flies avoid bitter substances, suggesting that Gr66a neuron activity is sufficient to mediate avoidance behavior. This receptor is required for sensing and avoiding N,N-Diethyl-meta-toluamide (DEET), the most widely used insect repellent worldwide, as well as L-canavanine, a plant-derived insecticide. Gr66a neurons are also involved in the sex-specific perception of molecules inducing male avoidance behavior, probably through sensing 7-tricosene (7-T), a male cuticular pheromone and leading to inhibition of male-male courtship.

Gr66a of Drosophila melanogaster (fruit fly)

The pheromone receptor, Or-1 (Nakagawa et al., 2012)

Animals

Or-1 of Bombyx mori (Q5WA61)

Sex pheromone receptor of 416 aas and 7 TMSs (Miura et al. 2010).

Insects

pheromone receptor of Ostrinia nubilalis (European corn borer) (Pyralis nubilalis)

Odorant receptor 3, Or3 of 410 aas and 7 TMSs.

Insects

Or3 of Epiphyas postvittana (Light brown apple moth)

Odorant (pheromone) receptor, OR-3, BmOR3, Or-3, PR-3, of 439 aas and 7 TMSs in a 2 + 1 + 2 + 2 TMS arrangement. The activation of PRs is coupled to the calcium permeability of their coreceptor (Orco (see TC# 1.A.69.1.1)) or putatively with G proteins (Lin et al. 2021). Using the PR BmOR3 from the silk moth B. mori and its coreceptor BmOrco as a template, Lin et al. 2021 showed that an agonist-induced conformational change of BmOR3 is transmitted to BmOrco through TMS7s of both receptors, resulting in the activation of BmOrco. Key interactions, including an ionic lock and a hydrophobic zipper, are essential for mediating the functional coupling between BmOR3 and BmOrco. BmOR3 also selectively coupled with Gi proteins, which is dispensable for BmOrco coupling. Moreover, trans-7TM BmOR3 recruited arrestin (see TC# 8.A.136) in an agonist-dependent manner, which indicated an important role for BmOR3-BmOrco complex formation in ionotropic functions. Thus, the coupling of G protein and arrestin to a prototype trans-7TMS PR, BmOR3, has been demonstrated (Lin et al. 2021).

OR3 of Bombyx mori (Silk moth)

Odorant receptor 85b (or85b) of 302 aas and 5 putative TMSs.  Binds the odorant, heptanone, for activation; 2-nananone is a competitive antagonist.  The second half of TMS3 is involved in odorant binding and activation (Nichols and Luetje 2010).

animals (Invertebrates; insects)

Or85b of Drosophila melanogaster

Odorant Receptor 4, OR4 or GPROR4, of 406 aas and 7 or 8 TMSs; if 8, the C-terminal TMS may not be a TMS. This odorant receptor specifically recognizes the human odorant sulcatone (6-methylhept-5-en-2-onesul), a volatile odorant emitted at uniquely high levels in humans, thereby playing a key role in mosquito's preference in biting human compared to other animals (McBride et al. 2014). Aedes aegypti is a vector for viruses that spread diseases like dengue, Zika and Chikungunya. Tiwari and Sowdhamini 2023 have modeled the full-length structure of OR4 and the ORco of A. aegypti.

OR4 of Aedes aegypti (Yellowfever mosquito; Culex aegypti)

Odorant receptor 22 of 312 aas and 6 TMSs

Insects

Or22 of Bombyx mori

Odorant receptor 17 of 401 aas and 8 TMSs

Insects

Or17 of Bombyx mori (Silk moth)

Odorant recpetor 278 if 385 aas and 8 TMSs

Insects

Or278 of Tribolium castaneum (Red flour beetle)

Odorant receptor 205 of 406 aas and 9 putative TMSs.

Insects

Or205 of Tribolium castaneum (Red flour beetle)