小柯机器人

山东大学孙金鹏等研究人员合作揭示哺乳动物嗅觉受体感知胺类气味的结构基础。2023年5月24日，《自然》杂志在线发表了这项成果。

研究人员报告了小鼠TAAR9（mTAAR9）和mTAAR9-G_s或mTAAR9-G_olf三聚体与β-苯乙胺、N,N-二甲基环己胺或亚精胺复合物的冷冻电镜结构。mTAAR9结构包含一个深而紧的配体结合口袋，该口袋由一个保守的D^3.32W^6.48Y^7.43模体装饰，对胺类气味识别至关重要。在mTAAR9结构中，连接N端和ECL2的独特二硫键是激动剂诱导的受体激活所需的。研究人员确定了TAAR家族成员检测单胺和多胺的关键结构模体，以及不同TAAR成员负责识别同一气味化学品的共享序列。研究人员通过结构表征和突变分析阐明了mTAAR9与G_s和G_olf偶联的分子基础。

总之，这些结果为胺类嗅觉受体的气味检测、受体激活和G_olf偶联提供了结构基础。

据介绍，在哺乳动物的鼻上皮中，气味被两个G蛋白偶联受体家族检测为气味，即气味受体和微量胺相关受体（TAAR）。TAAR是在有颌鱼和无颌鱼分化后出现的，包括一个大型的单系受体家族，识别挥发性胺类气味剂，进而引起种内和种间的先天行为，如吸引和厌恶。

附：英文原文

Title: Structural basis of amine odorant perception by a mammal olfactory receptor

Author: Guo, Lulu, Cheng, Jie, Lian, Shuo, Liu, Qun, Lu, Yan, Zheng, Yuan, Zhu, Kongkai, Zhang, Minghui, Kong, Yalei, Zhang, Chao, Rong, Naikang, Zhuang, Yuming, Fang, Guoxing, Jiang, Jingjing, Zhang, Tianyao, Han, Xiang, Liu, Zili, Xia, Ming, Liu, Shangming, Zhang, Lei, Liberles, Stephen D., Yu, Xiao, Xu, Yunfei, Yang, Fan, Li, Qian, Sun, Jin-Peng

Issue&Volume: 2023-05-24

Abstract: Odorants are detected as smell in the nasal epithelium of mammals by two G-protein-coupled receptor families, the odorant receptors and the trace amine-associated receptors1,2 (TAARs). TAARs emerged following the divergence of jawed and jawless fish, and comprise a large monophyletic family of receptors that recognize volatile amine odorants to elicit both intraspecific and interspecific innate behaviours such as attraction and aversion3,4,5. Here we report cryo-electron microscopy structures of mouse TAAR9 (mTAAR9) and mTAAR9–Gs or mTAAR9–Golf trimers in complex with β-phenylethylamine, N,N-dimethylcyclohexylamine or spermidine. The mTAAR9 structures contain a deep and tight ligand-binding pocket decorated with a conserved D3.32W6.48Y7.43 motif, which is essential for amine odorant recognition. In the mTAAR9 structure, a unique disulfide bond connecting the N terminus to ECL2 is required for agonist-induced receptor activation. We identify key structural motifs of TAAR family members for detecting monoamines and polyamines and the shared sequence of different TAAR members that are responsible for recognition of the same odour chemical. We elucidate the molecular basis of mTAAR9 coupling to Gs and Golf by structural characterization and mutational analysis. Collectively, our results provide a structural basis for odorant detection, receptor activation and Golf coupling of an amine olfactory receptor.

DOI: 10.1038/s41586-023-06106-4

Source: https://www.nature.com/articles/s41586-023-06106-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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