Odorant Receptor 7D4 Activation Dynamics

• DOI: 10.1002/ange.201713065
• Publication Date: 2018-02-21T19:54:39Z
• Authors: Claire A. de March; Jérémie Topin; Elise Bruguera; Gleb Novikov; Kentaro Ikegami; Hiroaki Matsunami; Jérôme Golebiowski
• Keywords: MECHANISM; 0301 basic medicine; 570; 0303 health sciences; functional assays; molecular modeling; olfactory receptors; RECOGNITION; Molecular Conformation; STRUCTURAL INSIGHTS; Molecular Dynamics Simulation; 540; Crystallography, X-Ray; Receptors, Odorant; molecular dynamics; FAMILY; 03 medical and health sciences; PROTEIN-COUPLED RECEPTORS; REVEALS; Humans; activation

Abstract Deciphering how an odorant activates receptor (OR) and changes in specific OR residues affect its responsiveness are central to understanding our sense of smell. A joint approach combining site‐directed mutagenesis functional assays with computational modeling has been used explore the signaling mechanics OR7D4. In this OR, a genetic polymorphism affects perception androstenone. Molecular simulations totaling 0.12 ms predicted that, similarly observations for other G‐protein‐coupled receptors known experimental structures, activation pathway connects ligand G‐protein binding site. The 3D model mechanism correlates vitro data notably predicts that OR7D4 WM variant is not activated. Upon activation, OR‐specific sequence motif convergence point mechanism. Our study suggests robust homology can serve as powerful tool capture dynamics related smell perception.