Probing the optimal architecture and molecular mechanism of insect odorant receptor heteromeric channels

Abstract Insects have a powerful olfactory system that is far more selective and sensitive than artificial detectors. Insect odorant receptors (ORs) are key components of the system, which are ligand-gated ion channels comprising a specific odorant-sensing OR and a highly conserved odorant receptor...

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Main Authors: Wei Xue, Xiao-Li Lu, Tian-Min Zhang, Yi Guo, Yong-Hu Li, Gang Li, Chang Xu, Hui-Meng Lu
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08572-0
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author Wei Xue
Xiao-Li Lu
Tian-Min Zhang
Yi Guo
Yong-Hu Li
Gang Li
Chang Xu
Hui-Meng Lu
author_facet Wei Xue
Xiao-Li Lu
Tian-Min Zhang
Yi Guo
Yong-Hu Li
Gang Li
Chang Xu
Hui-Meng Lu
author_sort Wei Xue
collection DOAJ
description Abstract Insects have a powerful olfactory system that is far more selective and sensitive than artificial detectors. Insect odorant receptors (ORs) are key components of the system, which are ligand-gated ion channels comprising a specific odorant-sensing OR and a highly conserved odorant receptor co-receptor (Orco). However, the stoichiometric ratios of the heterotetramers remain inconclusive, and the molecular mechanism by which the ligand initiates channel opening is still not fully understood. The present study is based on the technical approach of molecular dynamics (MD) simulation. We predict the spatial structures of locust LmOR35-Orco heterotetramer under various stoichiometric ratios, construct it within a membrane environment, and compare the structural changes of LmOR35-Orco before and after ligand binding. Furthermore, we analyze the molecular mechanism of LmOR35-Orco across different architectures. Our findings propose an optimal architecture (1OR:3Orco) for insect heteromeric odorant receptors, elucidate the molecular mechanism underlying receptor activation due to ligand-induced ion channel opening, and identify critical residues involved in ligand recognition and ion channel gating. This study provides valuable insights into the regulatory mechanism of insect olfaction and has significant implications for function modification and the development of bionic electronic noses.
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spelling doaj-art-4068ae0a059c4201a6a66822fe256a742025-08-20T03:05:56ZengNature PortfolioCommunications Biology2399-36422025-07-018111310.1038/s42003-025-08572-0Probing the optimal architecture and molecular mechanism of insect odorant receptor heteromeric channelsWei Xue0Xiao-Li Lu1Tian-Min Zhang2Yi Guo3Yong-Hu Li4Gang Li5Chang Xu6Hui-Meng Lu7School of Life Sciences, Northwestern Polytechnical UniversitySchool of Engineering, Xi’an International UniversitySchool of Life Sciences, Northwestern Polytechnical UniversitySchool of Life Sciences, Northwestern Polytechnical UniversityPherobio Semiochemical InstituteCollege of Life Sciences, Shaanxi Normal UniversityCollege of Life Sciences, Shaanxi Normal UniversitySchool of Life Sciences, Northwestern Polytechnical UniversityAbstract Insects have a powerful olfactory system that is far more selective and sensitive than artificial detectors. Insect odorant receptors (ORs) are key components of the system, which are ligand-gated ion channels comprising a specific odorant-sensing OR and a highly conserved odorant receptor co-receptor (Orco). However, the stoichiometric ratios of the heterotetramers remain inconclusive, and the molecular mechanism by which the ligand initiates channel opening is still not fully understood. The present study is based on the technical approach of molecular dynamics (MD) simulation. We predict the spatial structures of locust LmOR35-Orco heterotetramer under various stoichiometric ratios, construct it within a membrane environment, and compare the structural changes of LmOR35-Orco before and after ligand binding. Furthermore, we analyze the molecular mechanism of LmOR35-Orco across different architectures. Our findings propose an optimal architecture (1OR:3Orco) for insect heteromeric odorant receptors, elucidate the molecular mechanism underlying receptor activation due to ligand-induced ion channel opening, and identify critical residues involved in ligand recognition and ion channel gating. This study provides valuable insights into the regulatory mechanism of insect olfaction and has significant implications for function modification and the development of bionic electronic noses.https://doi.org/10.1038/s42003-025-08572-0
spellingShingle Wei Xue
Xiao-Li Lu
Tian-Min Zhang
Yi Guo
Yong-Hu Li
Gang Li
Chang Xu
Hui-Meng Lu
Probing the optimal architecture and molecular mechanism of insect odorant receptor heteromeric channels
Communications Biology
title Probing the optimal architecture and molecular mechanism of insect odorant receptor heteromeric channels
title_full Probing the optimal architecture and molecular mechanism of insect odorant receptor heteromeric channels
title_fullStr Probing the optimal architecture and molecular mechanism of insect odorant receptor heteromeric channels
title_full_unstemmed Probing the optimal architecture and molecular mechanism of insect odorant receptor heteromeric channels
title_short Probing the optimal architecture and molecular mechanism of insect odorant receptor heteromeric channels
title_sort probing the optimal architecture and molecular mechanism of insect odorant receptor heteromeric channels
url https://doi.org/10.1038/s42003-025-08572-0
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