美国杜克大学Hiroaki Matsunami等研究人员合作发现，工程化气味受体揭示气味辨别的基础。相关论文于2024年10月30日在线发表于国际学术期刊《自然》。

研究人员通过使用工程化的气味受体（OR），利用共识蛋白设计策略，揭示了气味-OR相互作用的分子特性。由于这些共识OR（consOR）源于人类17个主要亚家族，它们为建模个体本土OR提供了高序列和结构同源性的模板。

consOR的生化可操作性使得研究人员能够确定，四种具有特定配体识别特性的不同consOR的低温电子显微镜结构。I类consOR consOR51的结构与原生人类受体OR51E2显示出高度结构相似性，并生成了相关成员的同源模型，具有高预测能力。三种II类consOR的结构揭示了I类和II类OR之间气味结合和激活机制的不同模式。因此，consOR的结构为理解OR超家族对气味的分子识别奠定了基础。

研究人员表示，嗅觉系统如何检测和区分具有多样物理化学性质，和分子构型的气味仍然不太清楚。脊椎动物通过G蛋白偶联OR感知气味。在人类中，大约有400个OR使嗅觉成为可能。OR家族包括两个主要类别：I类OR对羧酸敏感，而II类OR则响应多种气味，代表了人类OR的主要组成部分。理解嗅觉的一个基本挑战是无法可视化气味与OR的结合。

附：英文原文

Title: Engineered odorant receptors illuminate the basis of odour discrimination

Author: de March, Claire A., Ma, Ning, Billesblle, Christian B., Tewari, Jeevan, Llinas del Torrent, Claudia, van der Velden, Wijnand J. C., Ojiro, Ichie, Takayama, Ikumi, Faust, Bryan, Li, Linus, Vaidehi, Nagarajan, Manglik, Aashish, Matsunami, Hiroaki

Issue&Volume: 2024-10-30

Abstract: How the olfactory system detects and distinguishes odorants with diverse physicochemical properties and molecular configurations remains poorly understood. Vertebrate animals perceive odours through Gprotein-coupled odorant receptors (ORs)1. In humans, around 400 ORs enable the sense of smell. The OR family comprises two main classes: classI ORs are tuned to carboxylic acids whereas classII ORs, which represent most of the human repertoire, respond to a wide variety of odorants2. A fundamental challenge in understanding olfaction is the inability to visualize odorant binding to ORs. Here we uncover molecular properties of odorant–OR interactions by using engineered ORs crafted using a consensus protein design strategy3. Because such consensus ORs (consORs) are derived from the 17 major subfamilies of human ORs, they provide a template for modelling individual native ORs with high sequence and structural homology. The biochemical tractability of consORs enabled the determination of four cryogenic electron microscopy structures of distinct consORs with specific ligand recognition properties. The structure of a classI consOR, consOR51, showed high structural similarity to the native human receptor OR51E2 and generated a homology model of a related member of the human OR51 family with high predictive power. Structures of three classII consORs revealed distinct modes of odorant-binding and activation mechanisms between classI and classII ORs. Thus, the structures of consORs lay the groundwork for understanding molecular recognition of odorants by the OR superfamily.

DOI: 10.1038/s41586-024-08126-0

Source: https://www.nature.com/articles/s41586-024-08126-0