Biology subjects

Topin, J.

Publications and source records attributed to Topin, J..

6 recordsLinked to original sources

bioRxiv2026

Single-point mutation alters odorant receptor sensitivity associated with host plant specialization in Spodoptera moths

Host specialization in herbivorous insects is often associated with divergence in chemosensory abilities. Here, we investigated the possible contribution of odorant receptors (ORs) in host plant restriction in the lily moth Spodoptera picta, a species specialized on Amaryllidaceae. Manual annotation of S. picta ORs in its genome revealed a repertoire similar in size and composition to those of its polyphagous sister species, S. littoralis and S. litura, suggesting that specialization did not involve major gene loss or expansion in the lily moth. To assess functional divergence beyond gene number, we applied a large scaled structure-based virtual screening approach to the entire OR repertoires of these three Spodoptera species, generating ligand-binding profiles for 120,591 volatile compounds. Among 69 1:1:1 OR orthologs, 24 exhibited divergent predicted binding spectra. We pinpointed OR29 that we also found to be highly expressed in both male and female antennae of S. picta through a RNAseq approach. Functional assays demonstrated that S. picta OR29 acquired heightened sensitivity to limonene enantiomers, volatiles emitted by host Amaryllidaceae inflorescences. Site-directed mutagenesis revealed that a single amino acid substitution within the predicted binding region underlies this shift in sensitivity. These results show that host specialization in S. picta has not been accompanied by significant OR repertoire remodeling, but rather by subtle molecular changes that fine-tune receptor sensitivity to host-derived volatiles.

molecular biology↗

bioRxiv2025

High-Fidelity Tuning of Olfactory Mixture Distances in the Perceptual Space of Smell Through a Community Effort

A central goal in sensory science is to establish quantitative mappings between physical stimuli and perceptual responses. While such mappings are well characterized in vision and audition, they remain poorly defined in olfaction, limiting progress toward understanding the representations of smell. Predicting perceptual similarity between odor mixtures offers a promising route to formalize these relationships. To advance this effort, the DREAM (Dialogue for Reverse Engineering Assessment and Methods) Olfactory Mixtures Prediction Challenge assembled a curated, cross-study dataset describing the similarity of 507 mixture pairs and an unpublished test set of 46 mixture pairs. Teams competed to predict the perceptual similarity of mixture pairs, and then collaborated post-challenge to create an ensemble combining top-performing models that notably improves predictions over the existing state-of-the-art models. Moreover, ensemble model maintains high predictive accuracy in novel validation set. Our model provides a reproducible framework for neuroscientists, chemists, and engineers to compare odor mixtures and provides a foundation for future efforts towards better understanding the olfactory properties of mixtures.

neuroscience↗

bioRxiv2024

Accelerating Ligand Discovery for Insect Odorant Receptors

Odorant receptors (ORs) are main actors of the insects peripheral olfactory system, making them prime targets for pest control through olfactory disruption. Traditional methods employed in the context of chemical ecology for identifying OR ligands rely on analyzing compounds present in the insects environment or screening molecules with structures similar to known ligands. However, these approaches can be time-consuming and constrained by the limited chemical space they explore. Recent advances in OR structural understanding, coupled with scientific breakthroughs in protein structure prediction, have facilitated the application of structure-based virtual screening (SBVS) techniques for accelerated ligand discovery. Here, we report the first successful application of SBVS to insect ORs. We developed a unique workflow that combines molecular docking predictions, in vivo validation and behavioral assays to identify new behaviorally active volatiles for non-pheromonal receptors. This work serves as a proof of concept, laying the groundwork for future studies and highlighting the need for improved computational approaches. Finally, we propose a simple model for predicting receptor response spectra based on the hypothesis that the binding pocket properties partially encode this information, as suggested by our results on Spodoptera littoralis ORs.

bioinformatics↗

bioRxiv2023

Elucidating the structural basis for ligand binding and translocation in conserved insect odorant receptor co-receptors

In numerous insects, the olfactory receptor family forms a unique class of heteromeric cation channels. Recent progress in resolving the odorant receptor structures offers unprecedented opportunities for deciphering their molecular mechanisms of ligand recognition. Unexpectedly, these structures in apo or ligand-bound states did not reveal the pathway taken by the ligands between the extracellular space and the deep internal cavities. By combining molecular modeling with electrophysiological recordings, we identified amino acids involved in the dynamic entry pathway and the binding of VUAA1 to Drosophila melanogasters odorant receptor co-receptor (Orco). Our results provide new evidence for the exact location of the agonist binding site and a detailed and original mechanism of ligand translocation controlled by a network of conserved residues. These findings would explain the particularly high selectivity of Orcos for their ligands.

molecular biology↗

bioRxiv2021

Extracellular loop 2 of G protein-coupled olfactory receptors is critical for odorant recognition

G protein-coupled olfactory receptors (ORs) enable us to detect innumerous odorants. They are also ectopically expressed, emerging as attractive drug targets. ORs can be promiscuous or highly specific, which is part of Natures strategy for odor discrimination. This work demonstrates that the extracellular loop 2 (ECL2) plays critical roles in OR promiscuity and specificity. Using site-directed mutagenesis and molecular modeling, we constructed 3D OR models in which ECL2 forms a lid of the orthosteric pocket. ECL2 controls the shape and the volume of the odorant-binding pocket, maintains the pocket hydrophobicity and acts as a gatekeeper of odorant binding. The interplay between the specific orthosteric pocket and the variable, less specific ECL2 controls OR specificity and promiscuity. The 3D models enabled virtual screening of new OR agonists and antagonists, exhibiting 78% hit rate in cell assays. This approach can be generalized to structure-based ligand screening for other GPCRs that lack high-resolution 3D structures.

molecular biology↗

bioRxiv2020

Functional Microswitches of Mammalian G Protein-Coupled Bitter-Taste Receptors

Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCRs). The experimental structure of these receptors has yet to be determined, and key-residues controlling their function remain mostly unknown. We designed an integrative approach to improve comparative modeling of TAS2Rs. Using current knowledge on class A GPCRs and existing experimental data in the literature as constraints, we pinpointed conserved motifs to entirely re-align the amino-acid sequences of TAS2Rs. We constructed accurate homology models of human TAS2Rs. As a test case, we examined the accuracy of the TAS2R16 model with site-directed mutagenesis and in vitro functional assays. This combination of in silico and in vitro results clarify sequence-function relationships and identify the functional molecular switches that encode agonist sensing and downstream signaling mechanisms within mammalian TAS2Rs sequences. ClassificationBiological sciences, Computational biology, and bioinformatics

bioinformatics↗