嗅觉
G蛋白偶联受体
嗅觉感受器
受体
丙酸盐
气味
生物物理学
嗅觉系统
化学
生物
生物化学
细胞生物学
计算生物学
神经科学
作者
Christian B. Billesbølle,Claire A. de March,Wijnand J C van der Velden,Ning Ma,Jeevan Tewari,Claudia Llinás del Torrent,Linus Li,Bryan Faust,Nagarajan Vaidehi,Hiroaki Matsunami,Aashish Manglik
标识
DOI:10.1101/2022.12.20.520951
摘要
Abstract Our sense of smell enables us to navigate a vast space of chemically diverse odor molecules. This task is accomplished by the combinatorial activation of approximately 400 olfactory G protein-coupled receptors (GPCRs) encoded in the human genome 1–3 . How odorants are recognized by olfactory receptors (ORs) remains mysterious. Here we provide mechanistic insight into how an odorant binds a human olfactory receptor. Using cryogenic electron microscopy (cryo-EM), we determined the structure of active human OR51E2 bound to the fatty acid propionate. Propionate is bound within an occluded pocket in OR51E2 and makes specific contacts critical to receptor activation. Mutation of the odorant binding pocket in OR51E2 alters the recognition spectrum for fatty acids of varying chain length, suggesting that odorant selectivity is controlled by tight packing interactions between an odorant and an olfactory receptor. Molecular dynamics simulations demonstrate propionate-induced conformational changes in extracellular loop 3 to activate OR51E2. Together, our studies provide a high-resolution view of chemical recognition of an odorant by a vertebrate OR, providing insight into how this large family of GPCRs enables our olfactory sense.
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