Nature| 山东大学和上海交大研究团队合力揭秘哺乳动物嗅觉识别机制

山东大学和上海交大的研究团队最近在顶级期刊《自然》发表研究成果,通过解析小鼠嗅觉受体 mTAAR9 的结构,首次揭示了哺乳动物嗅觉识别气味分子的分子机制!这项研究将大大推进我们对嗅觉编码原理的理解。这项研究系统解析了嗅觉感知的分子机制,不仅推进了对嗅觉编码原理的认识,还为开发靶向嗅觉受体的新药提供了理论基础。 even酷毙了!

原来,嗅觉受体可以通过“组合编码”的方式识别不同的气味分子,这让动物能感知区分数万亿种气味。研究团队通过结构生物学研究,发现了嗅觉受体识别胺类气味分子的通用机制,以及嗅觉受体激活的关键结构“篝火”。

文章介绍mTAAR9 受体有一个特殊的结构,可以像锁匠一样准确识别不同的气味分子。研究者还发现,mTAAR9 受体激活需要一个独特的二硫键结构,就像一把启动键。这些发现为我们理解嗅觉感知过程提供了关键性的结构基础。该研究不仅让我们对神奇的嗅觉世界有了全新认识,也为开发靶向嗅觉受体的新药创造了契机。

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.

转自：“PaperRSS”微信公众号

如有侵权，请联系本站删除！