Exchanging ligand-binding specificity between a pair of mouse olfactory receptor paralogs reveals odorant recognition principles

Baud, Olivia; Yuan, Shuguang; Veya, Luc; Filipek, Sławomir; Vogel, Horst; Pick, Horst

doi:10.1038/srep14948

Cited by 27 publications

(36 citation statements)

References 47 publications

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“…One causative mechanism for differences in tuning breadth may be the size of the respective ligand-binding pockets. Baud et al suggested this for mouse receptors Olfr73 and Olfr74 [50]. Here, the ligand cavity size showed an accessible volume of 200 Å 3 for broadly tuned Olfr73, and 250 Å 3 for narrowly tuned Olfr74 [50].…”

Section: Introductionmentioning

confidence: 50%

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3

Haag

Ahmed

Reiss

et al. 2019

Cell. Mol. Life Sci.

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Sulfur-containing compounds within a physiological relevant, natural odor space, such as the key food odorants, typically constitute the group of volatiles with the lowest odor thresholds. The observation that certain metals, such as copper, potentiate the smell of sulfur-containing, metal-coordinating odorants led to the hypothesis that their cognate receptors are metalloproteins. However, experimental evidence is sparse-so far, only one human odorant receptor, OR2T11, and a few mouse receptors, have been reported to be activated by sulfur-containing odorants in a copper-dependent way, while the activation of other receptors by sulfur-containing odorants did not depend on the presence of metals. Here we identified an evolutionary conserved putative copper interaction motif CC/CSSH, comprising two copper-binding sites in TMH5 and TMH6, together with the binding pocket for 3-mercapto-2-methylpentan-1-ol in the narrowly tuned human receptor OR2M3. To characterize the copper-binding motif, we combined homology modeling, docking studies, site-directed mutagenesis, and functional expression of recombinant ORs in a cell-based, real-time luminescence assay. Ligand activation of OR2M3 was potentiated in the presence of copper. This effect of copper was mimicked by ionic and colloidal silver. In two broadly tuned receptors, OR1A1 and OR2W1, which did not reveal a putative copper interaction motif, activation by their most potent, sulfur-containing key food odorants did not depend on the presence of copper. Our results suggest a highly conserved putative copper-binding motif to be necessary for a copper-modulated and thiol-specific function of members from three subfamilies of family 2 ORs.

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Section: Introductionmentioning

confidence: 50%

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3

Haag

Ahmed

Reiss

et al. 2019

Cell. Mol. Life Sci.

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“…Given that mice and rats are more closely related to pouched rats than to squirrels, we expected that orthologous genes might follow this pattern. We assume these genes should be orthologous and bind similar odorants with similar structures due to their similar protein sequences, however, it could be that small changes in these genes create ORs that bind different odorants, or change perception in other ways [20,21,71]. Identification of these potentially conserved ORs is important for understanding how the OR repertoire might respond to evolutionary pressures over time.…”

Section: Additions To Our Knowledge About Olfaction and Or Repertoirementioning

confidence: 99%

“…Which ORs bind which odorants is still largely unknown, as there are a number of technical limitations for high-throughput screening methods for ligand identification [14,15]. Despite these limitations, research shows that related ORs within subfamily groups (and orthologous OR genes among taxa) tend to bind structurally similar ligands [16], though the selectiveness and level of response by individual OSNs may vary [9,[17][18][19][20][21]. Although OSNs only contain one type of OR, the OR can bind a range of odorants causing this olfactory information to be coded using a combinatorial method [21].…”

Section: Introductionmentioning

confidence: 99%

“…Despite these limitations, research shows that related ORs within subfamily groups (and orthologous OR genes among taxa) tend to bind structurally similar ligands [16], though the selectiveness and level of response by individual OSNs may vary [9,[17][18][19][20][21]. Although OSNs only contain one type of OR, the OR can bind a range of odorants causing this olfactory information to be coded using a combinatorial method [21]. For example, a molecule might activate OSNs only in specific changing concentrations, or in mixtures (or alone) [5,22].…”

Section: Introductionmentioning

confidence: 99%

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The giant pouched rat (Cricetomys ansorgei) olfactory receptor repertoire

2020

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For rodents, olfaction is essential for locating food, recognizing mates and competitors, avoiding predators, and navigating their environment. It is thought that rodents may have expanded olfactory receptor repertoires in order to specialize in olfactory behavior. Despite being the largest clade of mammals and depending on olfaction relatively little work has documented olfactory repertoires outside of conventional laboratory species. Here we report the olfactory receptor repertoire of the African giant pouched rat (Cricetomys ansorgei), a Muroid rodent distantly related to mice and rats. The African giant pouched rat is notable for its large cortex and olfactory bulbs relative to its body size compared to other sympatric rodents, which suggests anatomical elaboration of olfactory capabilities. We hypothesized that in addition to anatomical elaboration for olfaction, these pouched rats might also have an expanded olfactory receptor repertoire to enable their olfactory behavior. We examined the composition of the olfactory receptor repertoire to better understand how their sensory capabilities have evolved. We identified 1145 intact olfactory genes, and 260 additional pseudogenes within 301 subfamilies from the African giant pouched rat genome. This repertoire is similar to mice and rats in terms of size, pseudogene percentage and number of subfamilies. Analyses of olfactory receptor gene trees revealed that the pouched rat has 6 expansions in different subfamilies compared to mice, rats and squirrels. We identified 81 orthologous genes conserved among 4 rodent species and an additional 147 conserved genes within the Muroid rodents. The orthologous genes shared within Muroidea suggests that there may be a conserved Muroid-specific olfactory receptor repertoire. We also note that the description of this repertoire can serve as a complement to other studies of rodent olfaction, as the pouched rat is an outgroup within Muroidea. Thus, our data suggest that African giant pouched rats are capable of both natural and trained olfactory behaviors with a typical Muriod olfactory receptor repertoire.

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“…In mammalian OSNs, both chemosensitivity and mechanosensitivity depends upon the Odorant Receptor (OR) they express . While odor‐dependent activation of these G protein‐coupled receptors (GPCRs) is, at least partly, understood , the molecular basis of their mechanosensitivity is less clear. One hypothesis is that mechanical stimuli deform OSN membranes to modulate the spontaneous (i.e.…”

Section: Polymodal Chemosensory and Mechanosensory Neurons And Receptorsmentioning

confidence: 99%

Multisensory neural integration of chemical and mechanical signals

Sánchez-Alcañiz

Benton

2017

BioEssays

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Chemosensation and mechanosensation cover an enormous spectrum of processes by which animals use information from the environment to adapt their behavior. For pragmatic reasons, these sensory modalities are commonly investigated independently. Recent advances, however, have revealed numerous situations in which they function together to control animals' actions. Highlighting examples from diverse vertebrates and invertebrates, we first discuss sensory receptors and neurons that have dual roles in the detection of chemical and mechanical stimuli. Next we present cases where peripheral chemosensory and mechanosensory pathways are discrete but intimately packaged to permit coordinated reception of external cues. Finally, we consider how chemical and mechanical signals converge in central neural circuitry to enable multisensory integration. These insights demonstrate how investigation of the interplay between different sensory modalities is key to a more holistic and realistic understanding of sensory-guided behaviors.

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Exchanging ligand-binding specificity between a pair of mouse olfactory receptor paralogs reveals odorant recognition principles

Cited by 27 publications

References 47 publications

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3

The giant pouched rat (Cricetomys ansorgei) olfactory receptor repertoire

Multisensory neural integration of chemical and mechanical signals

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