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研究揭示昆虫嗅觉受体识别不同气味的分子机制
2021-08-08 12:20

美国洛克菲勒大学Ruta, Vanessa研究团队的最新研究揭示了昆虫嗅觉受体识别气味的结构基础。相关论文于2021年8月4日发表在《自然》杂志上。

在本研究中,研究人员提出了关于个体嗅觉受体如何灵活识别不同气味的结构和分子机制。研究人员发现跳跃bristletail4 Machilis hrabei嗅觉受体MhOR5可组装为同四聚体气味门控离子通道,其具有广泛的化学适应性。使用冷冻电镜,研究人员解析了MhOR5在多个门控状态下的结构,单独以及与两种激动剂(气味丁香酚和驱虫剂避蚊胺)结合的复合结构。

这两种配体都可以被位于每个亚基跨膜区域相同几何结合口袋内的分布式疏水相互作用所识别,揭示了该受体对复杂化学物质敏感性的结构基础。结合袋内衬的单个残基突变可改变MhOR5对丁香酚和避蚊胺的敏感性,并广泛导致受体重配。总之,该研究数据支持以下模型,即不同气味刺激共享相同的结合结构,揭示了赋予嗅觉系统强大辨别能力的分子机制。

据介绍,嗅觉系统需要识别和区分种类繁多的气味。为了应对这一挑战,不同物种都采取了同一种策略,即通过嗅觉受体大家族的组合激活来编码气味特性,从而可以利用有限的受体识别广阔的化学世界。

附:英文原文

Title: The structural basis of odorant recognition in insect olfactory receptors

Author: del Mrmol, Josefina, Yedlin, Mackenzie A., Ruta, Vanessa

Issue&Volume: 2021-08-04

Abstract: Olfactory systems must detect and discriminate amongst an enormous variety of odorants1. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors1,2,3, thus allowing a finite number of receptors to detect a vast chemical world. Here we offer structural and mechanistic insight into how an individual olfactory receptor can flexibly recognize diverse odorants. We show that the olfactory receptor MhOR5 from the jumping bristletail4 Machilis hrabei assembles as a homotetrameric odorant-gated ion channel with broad chemical tuning. Using cryo-electron microscopy, we elucidated the structure of MhOR5 in multiple gating states, alone and in complex with two of its agonists—the odorant eugenol and the insect repellent DEET. Both ligands are recognized through distributed hydrophobic interactions within the same geometrically simple binding pocket located in the transmembrane region of each subunit, suggesting a structural logic for the promiscuous chemical sensitivity of this receptor. Mutation of individual residues lining the binding pocket predictably altered the sensitivity of MhOR5 to eugenol and DEET and broadly reconfigured the receptor’s tuning. Together, our data support a model in which diverse odorants share the same structural determinants for binding, shedding light on the molecular recognition mechanisms that ultimately endow the olfactory system with its immense discriminatory capacity.

DOI: 10.1038/s41586-021-03794-8

Source: https://www.nature.com/articles/s41586-021-03794-8

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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