10:00 - 12:00
Sat-S11
Goethe Hall
Chair/s:
Antonella Di Pizio, Sébastien Fiorucci
Computational approaches are widely used to get insights into the chemistry and biology of chemosensation. The ECRO Special Interest Group Computational Chemosensation aims to gather researchers working in computational chemosensation, to facilitate their interaction and advance computational techniques for chemical senses, but also promote the potential of computational works to promote collaborations with experimentalists. The proposed symposium is the first initiative of the group and aims to highlight computationally guided advancements in chemosensation, ranging from machine learning based predictors, to the use of computer-aided drug design tools for ligand discovery, to the multiscale simulations of chemosensory receptors, to network analyses of proteins and signaling events. Works on both taste and smell will be presented in the symposium. We expect that bringing together computational researchers from different fields will provide stimulating and fruitful discussions about future perspectives. Moreover, during the symposium, the ECRO special interest group will be introduced to the audience.
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Structural elucidation of mammalian odorant receptors
Sat-S11-004
Presented by: Claire A. de March
Claire A. de March 1, 2, Jeevan Tewari 1, Ning Ma 3, Christian Billesboelle 4, Wijnand Van Der Velden 3, Nagarajan Vaidehi 3, Aashish Manglik 4, Hiroaki Matsunami 1
1 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA, 2 Unit in Biological Sciences and Biotechnologies, Nantes University, Nantes, France, 3 City of Hope, Department Computational and Quantitative Medicine, Beckman Research Institute, Duarte, CA, USA, 4 University of California San Francisco, Department of Pharmaceutical Chemistry, San Francisco, CA, USA
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 allow us to attempt the first structural elucidation 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.

We thank the NIH for funding this research (CAdM K99DC01833; H.M, NV, AM R01DC020353)
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