Structural model for ligand binding and channel opening of an insect gustatory receptor.
J Biol Chem
; 298(11): 102573, 2022 11.
Article
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| MEDLINE
| ID: mdl-36209821
ABSTRACT
Insect gustatory receptors play roles in sensing tastants, such as sugars and bitter substances. We previously demonstrated that the BmGr9 silkworm gustatory receptor is a d-fructose-gated ion channel receptor. However, the molecular mechanism of how d-fructose could initiate channel opening were unclear. Herein, we present a structural model for a channel pore and a d-fructose-binding site in BmGr9. Since the membrane topology and oligomeric state of BmGr9 appeared to be similar to those of an insect odorant receptor coreceptor, Orco, we constructed a structural model of BmGr9 based on the cryo-EM Orco structure. Our site-directed mutagenesis data suggested that the transmembrane region 7 forms channel pore and controls channel gating. This model also suggested that a pocket formed by transmembrane helices 2 to 4 and 6 binds d-fructose. Using mutagenesis experiments in combination with docking simulations, we were able to determine the potent binding mode of d-fructose. Finally, based on these data, we propose a conformational change that leads to channel opening upon d-fructose binding. Taken together, these findings detail the molecular mechanism by which an insect gustatory receptor can be activated by its ligand molecule.
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1
Base de datos:
MEDLINE
Asunto principal:
Receptores Odorantes
/
Proteínas de Drosophila
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Biol Chem
Año:
2022
Tipo del documento:
Article