Class-wide sequence, structural, and docking-profile diversity of insect odorant receptors and structural specialization of Orco
- 1School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China
- 2College of Life Sciences, Shaanxi Normal University, Xi'an, China
Abstract
Insect olfaction is facilitated by a heterotetrameric odorant receptor–odorant receptor co-receptor (OR-Orco) complex. However, extensive sequence divergence and lineage-specific expansion have complicated large-scale comparisons of OR repertoires across insects. Here, we integrated sequence similarity, structural similarity, and molecular docking to analyze ORs from 115 insect species. OR repertoire size was associated with adult diet, larval diet, and habitat, but not with circadian rhythm. We developed a ‘trunk–branch’ network framework to classify ORs according to sequence and structural similarity and used large-scale molecular docking to derive comparative docking profiles. Despite marked differences in sequence- and structural-community composition, almost all sampled orders contained ORs assigned to all six docking-profile communities. Holometabolous insects showed higher OR sequence-community diversity than non-holometabolous insects, and docking-profile composition differed between extant lineages whose order-level origins predate or postdate the end-Permian mass extinction. Most notably, we identified a highly conserved extracellular β-sheet in Orco that restricts ligand access to the binding pocket and may contribute to its reduced capacity to bind natural odorants. The emergence of Orco represents a key evolutionary transition from homomeric receptors to heteromeric OR–Orco complexes, and our results suggest that this transition may have been accompanied by pronounced specialization of the extracellular domain and binding pocket. Together, these analyses provide a class-wide framework for comparing insect OR diversity and generate testable hypotheses for future experimental and evolutionary studies.
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BibTeX
@article{zhang2026classwide,
title = {{Class-wide sequence, structural, and docking-profile diversity of insect odorant receptors and structural specialization of Orco}},
author = {Tianmin Zhang and Xuanxiao Yang and Yufang Fu and Wei Xue and Yifeng Zhang and Suyang Duan and Yangming Yin and Yi Guo and Chenxi Gao and Yang Liu and Gang Li and Chang Xu and Huimeng Lu},
journal = {eLife},
year = {2026},
month = nov,
doi = {10.7554/elife.110877},
url = {https://elifesciences.org/articles/110877},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Class-wide sequence, structural, and docking-profile diversity of insect odorant receptors and structural specialization of Orco
AU - Tianmin Zhang
AU - Xuanxiao Yang
AU - Yufang Fu
AU - Wei Xue
AU - Yifeng Zhang
AU - Suyang Duan
AU - Yangming Yin
AU - Yi Guo
AU - Chenxi Gao
AU - Yang Liu
AU - Gang Li
AU - Chang Xu
AU - Huimeng Lu
PY - 2026
DA - 2026/11/03
JO - eLife
DO - 10.7554/elife.110877
UR - https://elifesciences.org/articles/110877
AB - Insect olfaction is facilitated by a heterotetrameric odorant receptor–odorant receptor co-receptor (OR-Orco) complex. However, extensive sequence divergence and lineage-specific expansion have complicated large-scale comparisons of OR repertoires across insects. Here, we integrated sequence similarity, structural similarity, and molecular docking to analyze ORs from 115 insect species. OR repertoire size was associated with adult diet, larval diet, and habitat, but not with circadian rhythm. We developed a ‘trunk–branch’ network framework to classify ORs according to sequence and structural similarity and used large-scale molecular docking to derive comparative docking profiles. Despite marked differences in sequence- and structural-community composition, almost all sampled orders contained ORs assigned to all six docking-profile communities. Holometabolous insects showed higher OR sequence-community diversity than non-holometabolous insects, and docking-profile composition differed between extant lineages whose order-level origins predate or postdate the end-Permian mass extinction. Most notably, we identified a highly conserved extracellular β-sheet in Orco that restricts ligand access to the binding pocket and may contribute to its reduced capacity to bind natural odorants. The emergence of Orco represents a key evolutionary transition from homomeric receptors to heteromeric OR–Orco complexes, and our results suggest that this transition may have been accompanied by pronounced specialization of the extracellular domain and binding pocket. Together, these analyses provide a class-wide framework for comparing insect OR diversity and generate testable hypotheses for future experimental and evolutionary studies.
SN - 2050-084X
ER -