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The structure of DmOR67d-DmOrco in the VUAA1-bound state
Structural highlights
FunctionOR67D_DROME Odorant receptor for the fatty-acid-derived male pheromone 11-cis vaccenyl acetate (cVA). Acts in concert with Snmp and lush to capture cVA molecules on the surface of Or67d expressing olfactory dendrites and facilitate their transfer to the odorant-receptor Orco complex. Necessary to mediate behavioral responses to cVA by regulating both male and female mating behavior. Activation of Or67d neurons by cVA inhibits courtship of other males, whereas in females their activation promotes receptivity to other males.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedPheromones mediate intraspecific communication to regulate the physiology and behavior of animals, particularly insects. The detection of pheromones is initiated by the binding of pheromone molecules, e.g., 11-cis-vaccenyl acetate (cVA) in Drosophila, to specific receptor proteins in chemosensory neurons, but the underlying molecular mechanisms remain unclear. Here, we report structures of Drosophila pheromone receptor OR67d-Orco complexes in apo closed, pheromone-bound open, and synthetic agonist VUAA1-bound open conformations. OR67d and Orco assemble into a hetero-tetrameric channel with a 1:3 stoichiometry. In OR67d, the inverted L-shaped cVA or its analog binds into a deep and bent hydrophobic pocket, inducing both local and global conformational changes that lead to an asymmetrical opening of the channel gate. By comparison, VUAA1 binds to Orco instead of OR67d to cause a similar asymmetrical opening. Together, our studies reveal the structural basis for pheromone activation of hetero-tetrameric pheromone receptors. Cryo-EM structures of Drosophila OR67d-Orco complexes reveal insect pheromone sensing mechanism.,Wang J, Yang C, Chang S, Jiao D, Lin J, Yang X, Cai W, Ma D, Ding ZJ, Huang J, Huang J, Fan M, Hu M, Wang Y, Xu H, Su N, Guo J Cell Res. 2026 Jun 10. doi: 10.1038/s41422-026-01264-2. PMID:42270979[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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