Structural elucidation and molecular mechanisms of mammalian odorant receptors

Odor perception is based on odorant receptors (ORs), which belong to the large family of G protein-coupled receptors and more particularly to the rhodopsin-like family, also called class A The vast majority of odorant receptors show poor cell surface expression in non-olfactory cells due to retention of the endoplasmic reticulum (ER), hindering their structural elucidation and functional study. Here, we study at the molecular level the expression mechanisms of this sub-family of G protein-coupled receptors. In this project, we use the diversity of the odorant receptor repertoire to create new optimized synthetic receptors based on their consensus sequences. Using these consensus ORs cases, we study the role of amino acids in their expression through molecular modeling, site-directed mutagenesis, and flow cytometry. Their functionality is also assessed by in vitro assays. We then developed a protocol to produce and purify the most promising ORs which allowed us to obtain the first structural elucidations of a mammalian OR. This research is crucial, not only to understand the strategy of our brain to perceive its olfactory environment but also to identify general mechanisms governing the function of ORs.