Ligands for pheromone-sensing neurons are not conformationally activated odorant binding proteins.

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_F7C6F265B863
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Ligands for pheromone-sensing neurons are not conformationally activated odorant binding proteins.
Périodique
PLoS Biology
Auteur(s)
Gomez-Diaz C., Reina J.H., Cambillau C., Benton R.
ISSN
1545-7885 (Electronic)
ISSN-L
1544-9173
Statut éditorial
Publié
Date de publication
2013
Volume
11
Numéro
4
Pages
e1001546
Langue
anglais
Résumé
Pheromones form an essential chemical language of intraspecific communication in many animals. How olfactory systems recognize pheromonal signals with both sensitivity and specificity is not well understood. An important in vivo paradigm for this process is the detection mechanism of the sex pheromone (Z)-11-octadecenyl acetate (cis-vaccenyl acetate [cVA]) in Drosophila melanogaster. cVA-evoked neuronal activation requires a secreted odorant binding protein, LUSH, the CD36-related transmembrane protein SNMP, and the odorant receptor OR67d. Crystallographic analysis has revealed that cVA-bound LUSH is conformationally distinct from apo (unliganded) LUSH. Recombinantly expressed mutant versions of LUSH predicted to enhance or diminish these structural changes produce corresponding alterations in spontaneous and/or cVA-evoked activity when infused into olfactory sensilla, leading to a model in which the ligand for pheromone receptors is not free cVA, but LUSH that is "conformationally activated" upon cVA binding. Here we present evidence that contradicts this model. First, we demonstrate that the same LUSH mutants expressed transgenically affect neither basal nor pheromone-evoked activity. Second, we compare the structures of apo LUSH, cVA/LUSH, and complexes of LUSH with non-pheromonal ligands and find no conformational property of cVA/LUSH that can explain its proposed unique activated state. Finally, we show that high concentrations of cVA can induce neuronal activity in the absence of LUSH, but not SNMP or OR67d. Our findings are not consistent with the model that the cVA/LUSH complex acts as the pheromone ligand, and suggest that pheromone molecules alone directly activate neuronal receptors.
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/06/2013 9:18
Dernière modification de la notice
20/08/2019 16:23
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