Cited 12 time in webofscience Cited 11 time in scopus

Odorant Receptor 7D4 Activation Dynamics

Title
Odorant Receptor 7D4 Activation Dynamics
Authors
deMarch, C.A.Topin, J.Bruguera, E.Novikov, G.Ikegami, K.Matsunami, H.Golebiowski, Jerome
DGIST Authors
deMarch, C.A.; Topin, J.; Bruguera, E.; Novikov, G.; Ikegami, K.; Matsunami, H.; Golebiowski, Jerome
Issue Date
2018-04
Citation
Angewandte Chemie - International Edition, 57(17), 4554-4558
Type
Article
Article Type
Article
Author Keywords
ActivationFunctional assaysMolecular dynamicsMolecular modelingOlfactory receptors
ISSN
1433-7851
Abstract
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.
URI
http://hdl.handle.net/20.500.11750/6209
DOI
10.1002/anie.201713065
Publisher
Wiley-VCH Verlag
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