Cited 6 time in
Cited 6 time in
Odorant Receptor 7D4 Activation Dynamics
- Odorant Receptor 7D4 Activation Dynamics
- deMarch, C.A.; Topin, J.; Bruguera, E.; Novikov, G.; Ikegami, K.; Matsunami, H.; Golebiowski, Jerome
- Issue Date
- Angewandte Chemie - International Edition, 57(17), 4554-4558
- Article Type
- Biochemistry; Molecular dynamics; Molecular modeling; Odors; Proteins; Activation mechanisms; Computational model; Functional assays; G protein coupled receptors; Genetic polymorphisms; Molecular simulations; Olfactory receptors; Site directed mutagenesis; Chemical activation
- Deciphering how an odorant activates an odorant receptor (OR) and how changes in specific OR residues affect its responsiveness are central to understanding our sense of smell. A joint approach combining site-directed mutagenesis and functional assays with computational modeling has been used to explore the signaling mechanics of OR7D4. In this OR, a genetic polymorphism affects our perception of androstenone. Molecular simulations totaling 0.12ms predicted that, similarly to observations for other G-protein-coupled receptors with known experimental structures, an activation pathway connects the ligand and the G-protein binding site. The 3D model activation mechanism correlates with in vitro data and notably predicts that the OR7D4 WM variant is not activated. Upon activation, an OR-specific sequence motif is the convergence point of the mechanism. Our study suggests that robust homology modeling can serve as a powerful tool to capture OR dynamics related to smell perception. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
- Wiley-VCH Verlag
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