Structural screens identify candidate human homologs of insect chemoreceptors and cryptic Drosophila gustatory receptor-like proteins
- University of Lausanne, Switzerland
Abstract
Insect Odorant receptors and Gustatory receptors define a superfamily of seven-transmembrane domain ligand-gated ion channels (referred to here as 7TMICs), with homologs identified across Animalia except Chordata. Previously, we used sequence-based screening methods to reveal conservation of this family in unicellular eukaryotes and plants (DUF3537 proteins) (Benton et al., 2020). Here we combine three-dimensional structure-based screening, ab initio protein folding predictions, phylogenetics and expression analyses to characterize additional candidate homologs with tertiary but little or no primary structural similarity to known 7TMICs, including proteins in disease-causing Trypanosoma. Unexpectedly, we identify structural similarity between 7TMICs and PHTF proteins, a deeply-conserved family of unknown function, whose human orthologs display enriched expression in testis, cerebellum and muscle. We also discover divergent groups of 7TMICs in insects, which we term the Gustatory receptor-like (Grl) proteins. Several Drosophila melanogaster Grls display selective expression in subsets of taste neurons, suggesting that they are previously-unrecognized insect chemoreceptors. Although we cannot exclude the possibility of remarkable structural convergence, our findings support the origin of 7TMICs in a eukaryotic common ancestor, counter previous assumptions of complete loss of 7TMICs in Chordata, and highlight the extreme evolvability of this protein fold, which likely underlies its functional diversification in different cellular contexts.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit flySCope, doi:10.1126/science.abk2432.
Article and author information
Author details
Nathaniel J Himmel
Funding
H2020 European Research Council (833548)
- Richard Benton
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030B-185377)
- Richard Benton
Human Frontier Science Program (LT-0003/2022-L)
- Nathaniel J Himmel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Claude Desplan, New York University, United States
Version history
- Preprint posted: December 15, 2022 (view preprint)
- Received: December 15, 2022
- Accepted: February 16, 2023
- Accepted Manuscript published: February 20, 2023 (version 1)
- Version of Record published: March 9, 2023 (version 2)
Copyright
© 2023, Benton & Himmel
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structural screens identify candidate human homologs of insect chemoreceptors and cryptic Drosophila gustatory receptor-like proteins
eLife 12:e85537.
https://doi.org/10.7554/eLife.85537
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