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The structural basis of odorant recognition in insect olfactory receptors

机译：昆虫嗅觉受体中气味识别的结构基础

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摘要

Olfactory systems must detect and discriminate amongst an enormous variety of odorants(1). 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 receptors(1-3), 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 bristletail(4) 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.
机译：嗅觉系统必须在各种各样的气味（1）中检测和歧视。为了应对这一挑战，各种各样的物种都融合了一种常见的策略，其中通过大型嗅觉受体的组合激活（1-3）的组合活化来编码气味同一性，因此允许有限数量的受体来检测庞大的化学世界。在这里，我们提供结构和机械洞察，进入单个嗅觉受体如何灵活地识别不同的气味剂。我们表明，来自跳跃的Bristletallail（4）Machilis Hrabei的嗅觉受体MHOR5作为具有广泛化学调谐的同型气味门通道组装。使用冷冻电子显微镜，我们阐明了多种胶片态的MHOR5结构，单独，与其两种激动剂 - 食味丁香酚和昆虫驱蚊器中的络合物。通过位于每个亚基的跨膜区域的相同几何简单结合口袋内的分布疏水相互作用来识别两个配体，表明该受体的混杂化学敏感性的结构逻辑。衬里衬里衬里的个体残留物的突变可预测地改变了MHOR5至丁香酚和DEET的敏感性，并广泛地重新配置了受体的调整。我们的数据支持一种模型，其中不同的气味分类具有相同的结构决定因素，用于结合的结合，脱落光的分子识别机制，最终赋予嗅觉系统的巨大歧视能力。

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  • 来源
    《Nature》 |2021年第7874期|126-131|共6页
  • 作者

    del Marmol Josefina; Yedlin Mackenzie A.; Ruta Vanessa;

  • 作者单位

    Rockefeller Univ Lab Neurophysiol & Behav 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Neurophysiol & Behav 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Neurophysiol & Behav 1230 York Ave New York NY 10021 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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