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Odorant Receptor 7D4 Activation Dynamics
Author(s) -
de March Claire A.,
Topin Jérémie,
Bruguera Elise,
Novikov Gleb,
Ikegami Kentaro,
Matsunami Hiroaki,
Golebiowski Jérôme
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201713065
Subject(s) - homology modeling , receptor , molecular dynamics , computational biology , mutagenesis , signal transduction , biophysics , biology , chemistry , microbiology and biotechnology , genetics , biochemistry , mutation , gene , computational chemistry , enzyme
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 0.12 ms 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.