Structural screens identify candidate human homologs of insect chemoreceptors and cryptic Drosophila gustatory receptor-like proteins.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_00D5F1CCFCD3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Structural screens identify candidate human homologs of insect chemoreceptors and cryptic Drosophila gustatory receptor-like proteins.
Journal
eLife
Author(s)
Benton R., Himmel N.J.
ISSN
2050-084X (Electronic)
ISSN-L
2050-084X
Publication state
Published
Issued date
20/02/2023
Peer-reviewed
Oui
Volume
12
Pages
e85537
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Insect odorant receptors and gustatory receptors define a superfamily of seven transmembrane domain 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.
Keywords
Animals, Humans, Drosophila melanogaster/metabolism, Drosophila Proteins/genetics, Drosophila Proteins/metabolism, Chemoreceptor Cells/metabolism, Insecta/metabolism, Phylogeny, Taste, Receptors, Odorant/genetics, Receptors, Odorant/metabolism, Insect Proteins/metabolism, D. melanogaster, chemosensory receptor, comparative genomics, evolutionary biology, genetics, genomics, human, insect, ion channel, phylogenetics, protein structure
Pubmed
Web of science
Open Access
Yes
Create date
12/12/2022 15:51
Last modification date
20/04/2023 6:08
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