A putative origin of the insect chemosensory receptor superfamily in the last common eukaryotic ancestor

Benton, Richard; Dessimoz, Christophe; Moi, David

doi:10.7554/elife.62507

Cited by 23 publications

(30 citation statements)

References 81 publications

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“…Anyhow, our work shows that reverse chemical ecology can be applied efficiently to identify behaviorally-active volatiles that could ultimately implement semiochemical-based control strategies against agricultural pests. Improved membrane protein tridimensional structure resolution [ 30 , 42 ] and prediction [ 43 , 44 ] will give access to structural details of the odorant-binding pocket of insect ORs then contributing to expand the chemical space to be explored by structure-based virtual screening.…”

Section: Discussionmentioning

confidence: 99%

Reverse chemical ecology in a moth: machine learning on odorant receptors identifies new behaviorally active agonists

Caballero-Vidal

Bouysset

Gévar

et al. 2021

Cell. Mol. Life Sci.

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The concept of reverse chemical ecology (exploitation of molecular knowledge for chemical ecology) has recently emerged in conservation biology and human health. Here, we extend this concept to crop protection. Targeting odorant receptors from a crop pest insect, the noctuid moth Spodoptera littoralis, we demonstrate that reverse chemical ecology has the potential to accelerate the discovery of novel crop pest insect attractants and repellents. Using machine learning, we first predicted novel natural ligands for two odorant receptors, SlitOR24 and 25. Then, electrophysiological validation proved in silico predictions to be highly sensitive, as 93% and 67% of predicted agonists triggered a response in Drosophila olfactory neurons expressing SlitOR24 and SlitOR25, respectively, despite a lack of specificity. Last, when tested in Y-maze behavioral assays, the most active novel ligands of the receptors were attractive to caterpillars. This work provides a template for rational design of new eco-friendly semiochemicals to manage crop pest populations.

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Section: Discussionmentioning

confidence: 99%

Reverse chemical ecology in a moth: machine learning on odorant receptors identifies new behaviorally active agonists

Caballero-Vidal

Bouysset

Gévar

et al. 2021

Cell. Mol. Life Sci.

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“…Gln467 is highly conserved across Orcos and ORs from M. hrabei and other basal insect species 32 and previously identified as a component of the only identified signature sequence motif (TYhhhhhQF) diagnostic of the highly divergent insect chemosensory receptor superfamily 34,35 . Mutation of Gln467 in MhOR5 to either the smaller residue, alanine, or the positively charged residue arginine, strongly impaired function, while a more conservative mutation to asparagine resulted in enhanced activity ( Fig.…”

Section: Odorant Binding Leads To Pore Openingmentioning

confidence: 94%

The structural basis of odorant recognition in insect olfactory receptors

Mármol

Yedlin

Ruta

2021

Preprint

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Olfactory systems must detect and discriminate an enormous diversity of chemicals in the environment. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors (ORs), thus allowing a finite number of receptors to detect an almost infinite chemical world. Although most individual ORs are sensitive to a variety of odorants, the structural basis for such flexible chemical recognition remains unknown. Here, we combine cryo-electron microscopy with functional studies of receptor tuning to gain insight into the structural and mechanistic basis of promiscuous odorant recognition. We show that OR5 from the jumping bristletail, Machilis hrabei, assembles as a homo-tetrameric odorant-gated ion channel with broad chemical tuning. We elucidated the structure of OR5 in multiple gating states, alone and in complex with two of its agonists—the odorant eugenol and the insect repellent DEET. Both ligands bind to a common binding site located in the transmembrane region of each subunit, composed of a simple geometric arrangement of aromatic and hydrophobic residues. We reveal that binding is mediated by hydrophobic, non-directional interactions with residues distributed throughout the binding pocket, enabling the flexible recognition of structurally distinct odorants. Mutation of individual residues lining the binding pocket predictably altered OR5’s sensitivity to eugenol and DEET and broadly reconfigured the receptor’s tuning, supporting a model in which diverse odorants share the same structural determinants for binding. Together, these studies provide structural insight into odorant detection, shedding light onto the molecular recognition mechanisms that ultimately endow the olfactory system with its immense discriminatory capacity.

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“…Ors are seven transmembrane domain proteins, a feature leading to long-held, incorrect assumptions that they were GPCRs. Rather, these proteins define a novel family of ion channels (figure 2), apparently absent in vertebrates, but with distant relatives (of unknown function) across invertebrates as well as in plants and unicellular eukaryotes [41][42][43][44]. Irs have evolved in protostomes from ionotropic glutamate receptors (iGluRs), a widely conserved family of ligand-gated ion channels bestknown for their roles at synapses in the central nervous system [20,45].…”

Section: Receptorsmentioning

confidence: 99%

“…Of particular note are the first structural explanations for how an olfactory receptor can be activated by chemically diverse ligands [35]. Such structures-as well as remarkably similar de novo models of other receptors (figure 2) [42]-synergize with analysis of natural sequence variation and site-directed mutagenesis [34,35,[47][48][49][50][51] to help define the molecular basis of receptor specificity and evolution. Irs may function similarly to their iGluR ancestors [30], and while no Ir structures are available, protein modelling in combination with mutational analyses have started to reveal principles of ligandrecognition and ion conduction of this family [30,[52][53][54].…”

Section: Receptorsmentioning

confidence: 99%

Drosophila olfaction: past, present and future

Benton

2022

Proc. R. Soc. B.

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Among the many wonders of nature, the sense of smell of the fly Drosophila melanogaster might seem, at first glance, of esoteric interest. Nevertheless, for over a century, the ‘nose’ of this insect has been an extraordinary system to explore questions in animal behaviour, ecology and evolution, neuroscience, physiology and molecular genetics. The insights gained are relevant for our understanding of the sensory biology of vertebrates, including humans, and other insect species, encompassing those detrimental to human health. Here, I present an overview of our current knowledge of D. melanogaster olfaction, from molecules to behaviours, with an emphasis on the historical motivations of studies and illustration of how technical innovations have enabled advances. I also highlight some of the pressing and long-term questions.

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A putative origin of the insect chemosensory receptor superfamily in the last common eukaryotic ancestor

Cited by 23 publications

References 81 publications

Reverse chemical ecology in a moth: machine learning on odorant receptors identifies new behaviorally active agonists

Reverse chemical ecology in a moth: machine learning on odorant receptors identifies new behaviorally active agonists

The structural basis of odorant recognition in insect olfactory receptors

Drosophila olfaction: past, present and future

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