Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRA, Univ. de Bourgogne- Franche-Comté, France.
Chem Senses. 2018 Feb 2;43(2):81-87. doi: 10.1093/chemse/bjx083.
The field of chemical senses has made major progress in understanding the cellular mechanisms of olfaction and taste in the past 2 decades. However, the molecular understanding of odor and taste recognition is still lagging far behind and will require solving multiple structures of the relevant full-length receptors in complex with native ligands to achieve this goal. However, the development of multiple complimentary strategies for the structure determination of G protein-coupled receptors (GPCRs) makes this goal realistic. The common conundrum of how multi-specific receptors that recognize a large number of different ligands results in a sensory perception in the brain will only be fully understood by a combination of high-resolution receptor structures and functional studies. This review discusses the first steps on this pathway, including biochemical and physiological assays, forward genetics approaches, molecular modeling, and the first steps towards the structural biology of olfactory and taste receptors.
在过去的 20 年里，化学感官领域在理解嗅觉和味觉的细胞机制方面取得了重大进展。然而，对气味和味觉识别的分子理解仍然远远落后，需要解决相关全长受体与天然配体复合的多个结构，才能实现这一目标。然而，多种互补的策略用于 G 蛋白偶联受体（GPCR）的结构测定，使得这一目标成为现实。只有通过高分辨率受体结构和功能研究的结合，才能充分了解多特异性受体识别大量不同配体如何导致大脑中的感觉感知这一常见难题。这篇综述讨论了这条途径的第一步，包括生化和生理学测定、正向遗传学方法、分子建模以及嗅觉和味觉受体结构生物学的初步步骤。
