Probing the optimal architecture and molecular mechanism of insect odorant receptor heteromeric channels
Wei Xue, Xiaoli Lu, Zhang Tian-min, Yi Guo, Y. Li, Gang Li, Chang Xu, Hui‐Meng Lu
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. The spatial structures, thermodynamic properties, and functional characterization of different architectures of insect odorant receptors reveal that the 1OR:3Orco stoichiometry is the optimal architecture for LmOR35, and that odorant receptor activation involves two molecular mechanisms — asymmetric mode and symmetric-like mode.